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EC number: 203-455-5 | CAS number: 107-03-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
There are no reproductive toxicity data for n-propyl mercaptan, (1-propanethiol; CAS 107-03-9), therefore data were read-across from the structurally analogous substance tert-butyl mercaptan (2-methylpropane-2-thiol; CAS 75-66-1).
In a combined repeated dose/reproductive/developmental toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP, the NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day (MHLW, 2006).
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- This study was classified as reliable with restriction because although it is a GLP guideline study, a study report in English was not available for data verification. However, this study is peer reviewed and considered sufficient for this endpoint.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- yes
- Remarks:
- The histopathological examination of the reproductive organs was only performed on 5 animals/sex of the control and top dose.
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 272.2-325.1 g for males, 188.1-235-9 g for females
- Housing:no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum):no data
- Acclimation period:no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-27
- Humidity (%): 35-75
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- no details available
- Duration of treatment / exposure:
- Exposure period: Males: 42 days; Females: 42-53 days from 14 days before mating to day 4 of lactation
Premating exposure period (males): 2 weeks
Premating exposure period (females): 2 weeks
Duration of test: 10, 50, 200 mg/kg bw/day - Frequency of treatment:
- Once daily
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Males: 12
Females: 17 for control and top dose, 12 for low and mid doses - Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
General condition was observed 2 or 3 times a day throughout the administration period
DETAILED CLINICAL OBSERVATIONS: Yes
Detailed clinical observation was carried out once a week in all animals throughout the administration period. In pregnant females, it was carried out on days 7, 14, and 20 of gestation and on day 4 of lactation. Sensory reaction test, grip strength, and motor activity were examined at 6 weeks of administration in males and on day 4 of lactation in pregnant females.
BODY WEIGHT: Yes
Body weights were measured on days 1 (before dosing), 4, 8, 11, 15, 18, 22, 25, 30, 32, 36, 39, and 42 of administration for males, For females, body weight was measured on days 1 (before dosing), 4, 8, 11, 15, 18, 22, 25, 30, 32, 36, 39, and 42 of administration, except for pregnant females for whom it was measured on days 0, 7, 14, and 20 of gestation and days 0 and 4 of lactation. Further, it was measured at necropsy in both sexes.
FOOD CONSUMPTION :
Food consumption was measured on days 1 (before dosing), 4, 8, 11, 15, 30, 32, 36, 39, and 42 of administration for males. For females, food consumption was measured on days 1 (before dosing), 4, 8, 11, 15, 30, 32, 36, 39, and 42 of administration, except for pregnant females for whom it was measured on days 1, 7, 14, and 20 of gestation and days 1 and 4 of lactation
WATER CONSUMPTION : No - Oestrous cyclicity (parental animals):
- yes
- Sperm parameters (parental animals):
- No
- Litter observations:
- STANDARDISATION OF LITTERS
Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead. - Postmortem examinations (parental animals):
- SACRIFICE
Necropsy was carried out at the day following the end of the administration and recovery periods
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
- The testis and epididymis of all males were weighed.
HISTOPATHOLOGY / ORGAN WEIGHTS
The testis, epididymis, prostate, and seminal vesicles of 5 males at 0 and 200 mg/kg bw/day were microscopically examined at the end of the administration period. Further, the ovary, uterus, and vagina of 5 females at 0 and 200 mg/kg bw/day were microscopically examined at the end of the administration period. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at 5 days of age.
- These animals were subjected to postmortem macroscopic examination for gross abnormalities. - Statistics:
- Statistical methods: X2 test was used for mating index, males and females fertility indices, gestation index, and delivery index were used. Wilcoxon Rank Sum Test Method for implantation index, death birth index, live birth index, and viability index on day 4 were used.
- Reproductive indices:
- Estrous cycle, number of copulated, number of pregnant females, mating length, mating index (# of pairs with successful copulation/# of pairs mating × 100), males or females fertility indices (# of pregnant animals/#of animals with successful mating×100), number of females with live pups, gestational length, number of corpora lutea, number of implantations, number of pups delivered, number of live pups delivered, gestation index (# of females with live pups/# of pregnant females × 100), implantation index (# of implants/# of corpora lutea × 100), delivery index (# of pups born/# of implants × 100), death birth index (number of stillborns/number of litter × 100), were determined.
- Offspring viability indices:
- Sex ratio, live birth index (# of live pups born/# of pups born × 100), and viability index on day 4 (# of live pups on postnatal day (PND) 4 /# of live pups born × 100) were determined.
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- >= 200 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Clinical signs:
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Histopathological findings:
- not examined
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 50 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: Decreased pup body weights
- Reproductive effects observed:
- not specified
- Conclusions:
- The test substance had no effects on any reproductive or developmental parameter. The NOAEL for reproductive and developmental toxicity was considered to be >= 200 mg/kg bw/day and the NOAEL for neonatal toxicity is considered to be 50 mg/kg/day.
- Executive summary:
In a combined repeated dose/reproductive/developmental toxicity screening test (OECD 422), groups of male and female Sprague-Dawley rats (12-17/sex/dose) were administered 2 -methylpropane-2 -thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated.
There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.
This study was classified as reliable with restriction because although it is a GLP guideline study, a study report in English was not available for data verification. However, this study is peer reviewed and considered sufficient for this endpoint.
Reference
A low body weight value was observed in both sexes at 200 mg/kg bw/day throughout the administration period. During the recovery period, a lower body weight was observed in females, but their body weight gains throughout the recovery period were similar to those of the control group.
A low food consumption value or a tendency toward a low value was observed in males at 200 mg/kg bw/day on days 4 and 15 of administration and in females at 200 mg/kg bw/day throughout the administration period. During the recovery period, females exhibited lower food consumption on day 1 of the recovery period, but food consumption after day 4 of the recovery period was similar to the control group. A decrease in food consumption was observed in females at 10mg/kg on day 15 of the administration period. However, it was not observed at 50mg/kg and not considered to be a dose-related effect.
ORGAN WEIGHTS (PARENTAL ANIMALS)
There were increases in relative weights of the testes and epididymides in males at 200 mg/kg. However, absolute weights of these organs were not changed, and no histopathological changes were observed in these organs. These changes were considered to be due to decreases in body weights.
Increases in absolute and relative weights of the epididymides were observed at 50mg/kg, but these changes were not considered to be dose related effects because these effects were not observed at 200 mg/kg bw/day.
Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day.
Reproductive performance of rats
Dose (mg/kg bw/day) |
0 |
10 |
50 |
200 |
Number of females eximaned |
12 |
12 |
12 |
12 |
Count of estrus |
3.67(0.78) |
3.92(0.29) |
3.83(0.58) |
3.83(0.39) |
Estrus cycle |
3.97(0.10) |
4.00(0.00) |
4.03(0.10) |
4.00(0.00) |
No. of pairs mating |
12 |
12 |
12 |
12 |
No. of pairs with successful mating |
12 |
12 |
12 |
12 |
No. of pregnant females |
12 |
12 |
12 |
11 |
Duration of mating |
2.75(1.42) |
3.33(2.84) |
3.58(3.18) |
3.36(1.80) |
Fertility index (%) |
100 |
100 |
100 |
91.67 |
Terminal delivery of F0 dams
Dose (mg/kg bw/day) |
0 |
10 |
50 |
200 |
No. of females with live pups |
12 |
12 |
12 |
11 |
Gestational length (day) |
22.08(0.29) |
22.50(0.52) |
22.33(0.65) |
22.18(0.40) |
# of corpora lutea |
15.08(2.11) |
14.58(2.61) |
15.67(2.15) |
15.36(1.96) |
# of implantation sites |
14.25(1.76) |
13.42(3.00) |
14.92(2.75) |
14.45(3.00) |
# of pups delivered |
13.75(1.82) |
13.08(3.34) |
14.08(3.20) |
13.64(2.77) |
Sex ratio (male/female) |
0.83 |
1.20 |
0.92 |
0.88 |
# of live pups on day 4 |
13.75(1.82) |
13.00(3.28) |
13.75(3.11) |
13.64(2.77) |
Viability index on day 4 |
98.79 |
98.08 |
96.97 |
99.33 |
Body weight of live newborns (g) |
||||
Male Day 0 |
6.4(0.5) |
6.9(0.6) |
6.7(0.7) |
6.2(0.2) |
Male Day 4 |
10.3(0.8) |
10.3(2.2) |
10.0(2.4) |
8.6(0.9)** |
Female Day 0 |
6.1(0.6) |
6.4(0.6) |
6.3(0.6) |
5.9(0.2) |
Female Day 4 |
9.8(0.9) |
9.8(2.0) |
9.5(2.4) |
8.2(0.9)** |
Number with external anomalies |
0 |
0 |
0 |
1 |
**:
P<0.01
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
There are no reproductive toxicity data for n-propyl mercaptan, (1-propanethiol; CAS 107-03-9), therefore data were read-across from the structurally analogous substance tert-butyl mercaptan (2-methylpropane-2-thiol; CAS 75-66-1). 1-Propanethiol and 2-methylpropane-2-thiol are characterised by an SH functional group with an aliphatic carbon chain. See attachment to Section 13 for justification of read-across.
In a combined repeated dose/reproductive/developmental toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP (MHLW, 2006), groups of male and female Sprague-Dawley rats (12-17/sex/dose) were administered 2 -methylpropane-2 -thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated.
There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.
Effects on developmental toxicity
Description of key information
There are no developmental toxicity data for n-propyl mercaptan, (1-propanethiol; CAS 107-03-9), therefore data were read-across from the structurally analogous substances tert-butyl mercaptan (2-methylpropane-2-thiol; CAS 75-66-1) and n-butyl mercaptan (1-butanethiol; CAS 109-79-5). 1-Propanethiol (NPM, target), 1-butanethiol (source) and 2-methylpropane-2-thiol (source) all contain a thiol (-SH) functional group with a branched or linear aliphatic carbon chain.
In a combined repeated dose/reproductive/developmental toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP, treatment with 2-methylpropane-2-thiol had no effects on any developmental parameter. The NOAEL for developmental toxicity was considered to be ≥200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day (MHLW, 2006).
In a prenatal developmental toxicity study according to OECD Test Guideline 414 and in compliance with GLP, treatment with 2-methylpropane-2-thiol by whole-body inhalation did not produce any teratogenic effects in rat. Therefore, the maternal and developmental NOAEC was determined to ≥195 ppm (the highest concentration tested) (Ulrich, 1982b).
In a prenatal developmental toxicity study according to OECD Test Guideline 414 and in compliance with GLP, treatment with 2-methylpropane-2-thiol by whole-body inhalation did not produce any teratogenic effects in mouse. Therefore, the maternal and developmental NOAEC was determined to ≥195 ppm (the highest concentration tested) (Ulrich, 1982b).
In a developmental toxicity study in rats, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, whole body inhalation exposure to the vapour concentrations of 0, 10, 68, and 152 ppm 1-butanethiol (0, 38, 255, and 570 mg/m3) for 6 hours/day during gestation days 6 to 19, did not result in any treatment-related adverse systemic or developmental effects in maternal animals and their pups. The NOAEC for maternal and developmental toxicity was concluded to be ≥152 ppm (≥570 mg/m3) based on no treatment-related effects at the highest concentration tested (Ulrich, 1982b; Thomas, 1987).
In a developmental toxicity study in mice, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, mortality was observed at 1-butanethiol concentrations of 68 and 152 ppm (0.26 and 0.58 mg/L); however, no foetal toxicity was observed in surviving animals. The NOAEC for maternal toxicity was 10 ppm (38 mg/m3) and ≥68 ppm (≥255 mg/m3) for developmental toxicity (Ulrich, 1982b; Thomas, 1987).
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2006
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- This study was classified as reliable with restriction because although it is a GLP guideline study, a study report in English was not available for data verification. However, this study is peer reviewed and considered sufficient for this endpoint.
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 422
- Deviations:
- yes
- Remarks:
- The histopathological examination of the reproductive organs was only performed on 5 animals/sex of the control and top dose.
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 272.2-325.1 g for males, 188.1-235-9 g for females
- Housing:no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum):no data
- Acclimation period:no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-27
- Humidity (%): 35-75
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- Exposure period: Males: 42 days; Females: 42-53 days from 14 days before mating to day 4 of lactation
Premating exposure period (males): 2 weeks
Premating exposure period (females): 2 weeks - Duration of treatment / exposure:
- Exposure period: Males: 42 days; Females: 42-53 days from 14 days before mating to day 4 of lactation
- Frequency of treatment:
- once daily
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Males: 12
Females: 17 for control and top dose, 12 for low and mid doses - Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
General condition was observed 2 or 3 times a day throughout the administration period
DETAILED CLINICAL OBSERVATIONS: Yes
Detailed clinical observation was carried out once a week in all animals throughout the administration period. In pregnant females, it was carried out on days 7, 14, and 20 of gestation and on day 4 of lactation. Sensory reaction test, grip strength, and motor activity were examined at 6 weeks of administration in males and on day 4 of lactation in pregnant females.
BODY WEIGHT: Yes
Body weights were measured on days 1 (before dosing), 4, 8, 11, 15, 18, 22, 25, 30, 32, 36, 39, and 42 of administration for males, For females, body weight was measured on days 1 (before dosing), 4, 8, 11, 15, 18, 22, 25, 30, 32, 36, 39, and 42 of administration, except for pregnant females for whom it was measured on days 0, 7, 14, and 20 of gestation and days 0 and 4 of lactation. Further, it was measured at necropsy in both sexes.
FOOD CONSUMPTION :
Food consumption was measured on days 1 (before dosing), 4, 8, 11, 15, 30, 32, 36, 39, and 42 of administration for males. For females, food consumption was measured on days 1 (before dosing), 4, 8, 11, 15, 30, 32, 36, 39, and 42 of administration, except for pregnant females for whom it was measured on days 1, 7, 14, and 20 of gestation and days 1 and 4 of lactation
WATER CONSUMPTION : No - Ovaries and uterine content:
- Examinations included:
- Gravid uterus weight: Yes / No / No data
- Number of corpora lutea: Yes
- Number of implantations: Yes - Fetal examinations:
- PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead. - Statistics:
- Statistical methods: X2 test was used for mating index, males and females fertility indices, gestation index, and delivery index were used. Wilcoxon Rank Sum Test Method for implantation index, death birth index, live birth index, and viability index on day 4 were used.
- Indices:
- Off-spring indices:
Sex ratio, live birth index (# of live pups born/# of pups born × 100), and viability index on day 4 (# of live pups on postnatal day (PND) 4 /# of live pups born × 100) were determined.
Reproductive indices:
Estrous cycle, number of copulated, number of pregnant females, mating length, mating index (# of pairs with successful copulation/# of pairs mating × 100), males or females fertility indices (# of pregnant animals/#of animals with successful mating×100), number of females with live pups, gestational length, number of corpora lutea, number of implantations, number of pups delivered, number of live pups delivered, gestation index (# of females with live pups/# of pregnant females × 100), implantation index (# of implants/# of corpora lutea × 100), delivery index (# of pups born/# of implants × 100), death birth index (number of stillborns/number of litter × 100), were determined. - Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
A low body weight value was observed in both sexes at 200 mg/kg bw/day throughout the administration period. During the recovery period, a lower body weight was observed in females, but their body weight gains throughout the recovery period were similar to those of the control group.
A low food consumption value or a tendency toward a low value was observed in males at 200 mg/kg bw/day on days 4 and 15 of administration and in females at 200 mg/kg bw/day throughout the administration period. During the recovery period, females exhibited lower food consumption on day 1 of the recovery period, but food consumption after day 4 of the recovery period was similar to the control group. A decrease in food consumption was observed in females at 10mg/kg on day 15 of the administration period. However, it was not observed at 50mg/kg and not considered to be a dose-related effect.
ORGAN WEIGHTS (PARENTAL ANIMALS)
There were increases in relative weights of the testes and epididymides in males at 200 mg/kg. However, absolute weights of these organs were not changed, and no histopathological changes were observed in these organs. These changes were considered to be due to decreases in body weights.
Increases in absolute and relative weights of the epididymides were observed at 50mg/kg, but these changes were not considered to be dose related effects because these effects were not observed at 200 mg/kg bw/day. - Dose descriptor:
- NOAEL
- Effect level:
- >= 50 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: Based on body weight reduction observed in female rats dosed at 200 mg/kg/day.
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. - Dose descriptor:
- NOAEL
- Effect level:
- >= 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The test substance had no effects on any developmental parameter. The NOAEL for developmental toxicity was considered to be >= 200 mg/kg bw/day and the NOAEL for neonatal toxicity is considered to be 50 mg/kg/day.
- Executive summary:
In a combined repeated dose/reproductive/developmental toxicity screening test (OECD 422), groups of male and female Sprague-Dawley rats (12-17/sex/dose) were administered 2-methylpropane-2-thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated.
There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.
This study was classified as reliable with restriction because although it is a GLP guideline study, a study report in English was not available for data verification. However, this study is peer reviewed and considered sufficient for this endpoint.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: The Charles River Breeding Laboratories Inc., Portage, Michigan, USA
- Age at study initiation: approximately 12 weeks old
- Weight at study initiation: 25-36 grams at the time of mating
- Housing: individually housed, except during mating, in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina® Certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 26 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Animal Exposure Methods:
Exposures were conducted in one cubic meter glass and stainless steel exposure chambers. Air for the chamber ventilation was supplied from a HVAC system separate from the general laboratory systems. This air was particulate filtered (99.9% + 0.3 µ) and controlled for temperature and humidity. Chamber airflow rate varied between 200 and 260 L/min depending on desired exposure concentrations.
Exposure chamber temperatures and relative humidity were recorded each day alter three and six hours of exposure. Table 1 presents the minimum and maximum and the mean temperature and relative humidity at the six hour measurement time for each group over the course of the study.
Exposure Atmosphere Generation Methods:
A vapor atmosphere of the test material was generated utilizing a counter-current vaporization system. This system operated as follows: The test material was pumped at a known and constant rate to the top of the bead column by a FMI® fluid metering pump or Sagee syringe drive.
Dry-compressed air passed up the bead column in a countercurrent manner relative to the liquid. Vaporization occurred on the bead column. The concentrated vapors were piped to the exposure chamber air inlet where dilution with chamber ventilation air reduced the concentration to the desired level. Table 2 summarizes the vapor generation system operating conditions. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Nominal exposure concentrations were calculated for all exposures. Actual exposure concentrations were measured by non-dispersive Infrared spectrophotometry utilizing a Wilks (MIRAN®) lA analyzer. The analyzer was calibrated by volumetric dilution of pure (99%) t-Butyl Mercaptan in saran gas bags. The calibration was checked once daily.
- Details on mating procedure:
- One female and one male animal of the same species and strain were placed together for mating. The occurrence of copulation was determined by daily inspection for a copulatory plug. The day evidence of mating was detected was designated day 0 of gestation and the female was returned to an individual cage.
- Duration of treatment / exposure:
- gestation days 6 - 16
- Frequency of treatment:
- 6 hour/day
- Duration of test:
- until GD17
- Dose / conc.:
- 10 ppm
- Remarks:
- desired conc.
- Dose / conc.:
- 100 ppm
- Remarks:
- desired conc.
- Dose / conc.:
- 200 ppm
- Remarks:
- desired conc.
- Dose / conc.:
- 11 ppm (analytical)
- Dose / conc.:
- 99 ppm (analytical)
- Dose / conc.:
- 195 ppm (analytical)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, sham-exposed
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
Prior to initiation of the treatment period all animals were observed twice daily for mortality and overt changes in appearance and behavior. All animals were observed daily for mortality and clinical signs of toxicity from gestation day 6 through sacrifice.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 15 and 17 .
FOOD CONSUMPTION: No
WATER CONSUMPTION : No
POST-MORTEM EXAMINATIONS: Yes
On gestation day 17, all surviving dams were sacrificed by carbon dioxide inhalation. The abdominal and thoracic cavities and organs of the dams were examined for grossly evident morphological changes and the carcasses discarded. Uteri from females that appeared nongravid were placed in 10% ammonium sulfide solution for confirmation of pregnancy. - Ovaries and uterine content:
- The ovaries and uterine content were examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was externally sexed and individually numbered and tagged for identification
- Soft tissue examinations: Yes
Approximately one-half of the fetuses were placed in Bouin's fixative for subsequent visceral examination by razor-blade sectioning as described by Wilson.
- Skeletal examinations: Yes
The remaining one-half of the fetuses were fixed in alcohol, macerated in potassium hydroxide and stained with Alizarin Red S by a method similar to that described by Dawson2 for subsequent skeletal examination
- Head examinations: No - Statistics:
- The male to female fetal sex distribution and the numbers of fetuses and litters with malformations were compared using the X2 test criterion with Yate's correction for 2X2 contingency tables and/or Fisher's exact probability test. The numbers of early and late resorptions, nonviable fetuses, and postimplantation loss were compared by the Mann-Whitney U test. The mean numbers of viable fetuses, total implantations, and corpora lutea, and mean fetal body weights were compared by analysis of variance (one way classification). Bartlett's test for homogeneity of variances, and the appropriate t test using Dunnett's multiple comparison tables were used to judge significance of differences. All statistical analyses compared the treatment group to the control group with the level of significance at p<0.05.
- Historical control data:
- See the attached file
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The livers of all female mice, preserved in 10% formalin as specified in the protocol, were externally normal. At 100 and 200 ppm, the mean absolute and relative liver weights were increased when compared to the control group (Table 6), but were not statistically significant and likely an adaptive response. The values et 10 ppm were comparable to the control group.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- corpora lutea
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Maternal Observations:
Survival was 100% in all groups. The mice in the treated groups were similar in appearance and behavior to the control group mice. No treatment-related trend in necropsy findings was observed. The livers of all female mice, preserved in 10% formalin as specified in the protocol, were externally normal. At 100 and 200 ppm, the mean absolute and relative liver weights were increased when compared to the control group (Table 6), but were not statistically significant and likely an adaptive response. The values et 10 ppm were comparable to the control group.
There were no biologically meaningful differences in mean maternal body weight (Table 4) during the treatment period (gestation days 6-17) or over the entire gestation period (gestation day 0-17) in the t-butyl Mercaptan treated mice when compared to the control group mice. In addition, the adjusted (dam weight on gestation day 17 minus the gravid uterus weight) mean maternal body weight change (Table 4) from gestation days 0-17 in the treated groups in this study segment was comparable to the control group.
Caesarean Section Observations:
There were no biologically meaningful or statistically significant differences in the mean number of viable fetuses, postimplantation loss, total implantations, corpora lutea, fetal body weight or the fetal sex distribution in the treated groups when compared to the control group (Table 5) and the historical control data. - Dose descriptor:
- NOAEC
- Effect level:
- >= 195 ppm (analytical)
- Basis for effect level:
- other: no observed effects
- Remarks on result:
- other:
- Remarks:
- Equivalent to 721 mg/m³
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not specified
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- An increase in the total litters with malformations, due primarily to the increased incidence of the malformation vertebral anomalies, was noted in the t-butyl mercaptan treated groups when compared to the control group. However, this incidence did not occur in a dose-related pattern (47.8% and 28.6% of the litters in the 100 and 200 ppm groups, respectively, had malformed fetuses) and was not statistically significant (p>0.05).
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Vertebral anomalies were present in 16.7% of the litters in both the control group and the 10 ppm group, in 43.5% of the litters in the group 100 ppm and in 23.8% of the litters in the 200 ppm. The only other malformation present in the 200 ppm group was a single instance of rib anomalies. In the 10 and 100 ppm groups, the remaining malformations did not occur in a dose-related pattern and/or were within the range of the historical control data.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- An increase in the percent of fetuses per group with the variations misaligned sternebrae and/or 14th rudimentary ribs was noted in the treated groups when compared to the control group. The incidence of misaligned sternebrae in the control and treated groups was greater than the highest value in the historical control data, while the occurrence of 14th rudimentary ribs in the control and treated groups was within the range of the historical control data. There were no other trends in the incidence of genetic or developmental variations in the treated groups when compared to the control group.
- Dose descriptor:
- NOAEC
- Effect level:
- >= 195 ppm (analytical)
- Sex:
- male/female
- Basis for effect level:
- other: no observed effects
- Remarks on result:
- other: Equivalent to 721 mg/m³
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- No teratogenic effects occurred in mice when administered 2-methylpropane-2-thiol by whole body inhalation at or below the 195 ppm actual exposure level.
- Executive summary:
Pregnant female mice (CD-1; 25/group) were repeatedly exposed (inhalation, whole body) to 2-methylpropane-2-thiol for 6 hrs/day during GD 6-16. Exposure conditions consisted of measured concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm). The study design was similar to OECD Test Guideline No. 414. All animals survived to scheduled termination. there were no statistically significant differences between the dosed animals and controls with respect to maternal endpoints. Fetal malformations were observed in mice exposed to 99 ppm (litter incidence, 47.8 %) and 195 ppm (litter incidence, 28.6%) when compared to the control group (litter incidence, 16.7%). The particular malformation noted (i.e., vertebral anomaly), however, did not increase in a dose-related pattern and was in the range of historical control data. There were no additional statistically significant differences in fetuses exposed to 2 -methylpropane-2-thiol when compared to controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when t-butyl mercaptan was administered by whole body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and fetal NOAEC was equal or higher than 195 ppm.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: The Charles River Breeding Laboratories Inc., Portage, Michigan, USA
- Age at study initiation: approximately 14 weeks old
- Weight at study initiation: 221-303 grams at the time of mating
- Housing: individually housed, except during mating, in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina® Certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 26 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Animal Exposure Methods:
Exposures were conducted in one cubic meter glass and stainless steel exposure chambers. Air for the chamber ventilation was supplied from a HVAC system separate from the general laboratory systems. This air was particulate filtered (99.9% + 0.3 µ) and controlled for temperature and humidity. Chamber airflow rate varied between 200 and 260 L/min depending on desired exposure concentrations.
Exposure chamber temperatures and relative humidity were recorded each day alter three and six hours of exposure. Table 1 presents the minimum and maximum and the mean temperature and relative humidity at the six hour measurement time for each group over the course of the study.
Exposure Atmosphere Generation Methods:
A vapor atmosphere of the test material was generated utilizing a counter-current vaporization system. This system operated as follows: The test material was pumped at a known and constant rate to the top of the bead column by a FMI® fluid metering pump or Sagee syringe drive.
Dry-compressed air passed up the bead column in a countercurrent manner relative to the liquid. Vaporization occurred on the bead column. The concentrated vapors were piped to the exposure chamber air inlet where dilution with chamber ventilation air reduced the concentration to the desired level. Table 2 summarizes the vapor generation system operating conditions. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Nominal exposure concentrations were calculated for all exposures. Actual exposure concentrations were measured by non-dispersive Infrared spectrophotometry utilizing a Wilks (MIRAN®) lA analyzer. The analyzer was calibrated by volumetric dilution of pure (99%) t-Butyl Mercaptan in saran gas bags. The calibration was checked once daily.
- Details on mating procedure:
- One female and one male animal of the same species and strain were placed together for mating. The occurrence of copulation was determined by daily inspection for a copulatory plug. The day evidence of mating was detected was designated day 0 of gestation and the female was returned to an individual cage.
- Duration of treatment / exposure:
- gestation days 6 - 19
- Frequency of treatment:
- 6 hour/day
- Duration of test:
- until GD20
- Dose / conc.:
- 10 ppm
- Remarks:
- target conc.
- Dose / conc.:
- 100 ppm
- Remarks:
- target conc.
- Dose / conc.:
- 200 ppm
- Remarks:
- target conc.
- Dose / conc.:
- 11 ppm (analytical)
- Dose / conc.:
- 99 ppm (analytical)
- Dose / conc.:
- 195 ppm (analytical)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, sham-exposed
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
Prior to initiation of the treatment period all animals were observed twice daily for mortality and overt changes in appearance and behavior. All animals were observed daily for mortality and clinical signs of toxicity from gestation day 6 through sacrifice.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 16 and 20.
FOOD CONSUMPTION: No
WATER CONSUMPTION : No
POST-MORTEM EXAMINATIONS: Yes
On gestation day 20, all surviving dams were sacrificed by carbon dioxide inhalation. The abdominal and thoracic cavities and organs of the dams were examined for grossly evident morphological changes and the carcasses discarded. Uteri from females that appeared nongravid were placed in 10% ammonium sulfide solution for confirmation of pregnancy. - Ovaries and uterine content:
- The ovaries and uterine content were examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was externally sexed and individually numbered and tagged for identification
- Soft tissue examinations: Yes
Approximately one-half of the fetuses were placed in Bouin's fixative for subsequent visceral examination by razor-blade sectioning as described by Wilson.
- Skeletal examinations: Yes
The remaining one-half of the fetuses were fixed in alcohol, macerated in potassium hydroxide and stained with Alizarin Red S by a method similar to that described by Dawson2 for subsequent skeletal examination
- Head examinations: No - Statistics:
- The male to female fetal sex distribution and the numbers of fetuses and litters with malformations were compared using the X2 test criterion with Yate's correction for 2X2 contingency tables and/or Fisher's exact probability test. The numbers of early and late resorptions, nonviable fetuses, and postimplantation loss were compared by the Mann-Whitney U test. The mean numbers of viable fetuses, total implantations, and corpora lutea, and mean fetal body weights were compared by analysis of variance (one way classification). Bartlett's test for homogeneity of variances, and the appropriate t test using Dunnett's multiple comparison tables were used to judge significance of differences. All statistical analyses compared the treatment group to the control group with the level of significance at p<0.05.
- Historical control data:
- See the attached file
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- An increase in the number of rats with hair loss on the limbs was noted in the treated groups when compared to the control group. Soft stool was observed in 10, 8, 9 and 8 rats in the 0, 10, 100 and 200 ppm groups. There were no other biologically meaningful differences in the appearance or behavior of rats between the treated and control groups.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no biologically meaningful differences in mean maternal body weight (Table 4) during the treatment period (gestation days 6-20) or over the entire gestation period (gestation days 0-20) in the t-butyl Mercaptan treated rats when compared to the control group rats.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- An increased post-implantation loss occurred in rats in the 200 ppm exposure group when compared to the control and mean values in the historical control data. These data may have been skewed by one animal having 14 (100%) postimplantation losses.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Dose descriptor:
- NOAEC
- Effect level:
- >= 195 ppm (analytical)
- Basis for effect level:
- clinical signs
- pre and post implantation loss
- Remarks on result:
- other:
- Remarks:
- Equivalent to 721 mg/m³
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A statistically significant increase in mean fetal body weight was noted in the group exposed to 10 ppm when compared to the control group; however, the value was within the range of the historical control data and was considered due to random occurrence.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean foetal body weights at the two highest dose groups exceeded the control value.
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Five fetuses in one litter in the 200 ppm dose group exhibited the external malformation of dwarfism. As dwarfism has been observed in several fetuses in a single litter in the historical control data this effect is believed to be of genetic origin in the testing laboratory and not considered treatment-related.
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- No relevant or statistically significant differences in the mean number of corpora lutea.
- Dose descriptor:
- NOAEC
- Effect level:
- >= 195 ppm (analytical)
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- Remarks on result:
- other:
- Remarks:
- Equivalent to 721 mg/m³
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- No teratogenic effects occurred in rats when administered 2-methylpropane-2-thiol by whole body inhalation at or below the 195 ppm actual exposure level.
- Executive summary:
Pregnant female rats (COBS CD; 25/group) were repeatedly exposed (inhalation, whole body) to 2-methylpropane-2-thiol for 6 hrs/day during gestational days (GD) 6-19. Exposure conditions consisted of measured concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm). The control group was exposed to filtered air only on a comparable regimen. Caesarean sections were performed on all surviving rats on gestation day 20. The study design was similar to OECD Test Guideline No. 414. All rats survived until study termination. During the in-life portion of the study, there was an increase in the number of rats with hair loss in the treated groups when compared to the control group; however, there were no other signs of maternal toxicity. At necropsy, there were no biologically relevant or statistically significant differences in the mean number of viable fetuses, total implantations, corpora lutea, or fetal sex distribution in the exposed groups as compared to controls. Fetal evaluations did not reveal biologically relevant or statistically significant differences in malformations among the dosed animals as compared to the controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when 2-methylpropane-2-thiol was administered by whole body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and fetal NOAEC was equal or higher than 195 ppm.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1982
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- limited information on animal husbandry and methods
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: The Charles River Breeding Laboratories Inc., Portage, Michigan, USA
- Age at study initiation: approximately 12 weeks old
- Weight at study initiation: 25-36 grams at the time of mating
- Housing: individually housed, except during mating, in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina® Certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 26 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: vapour
- Vehicle:
- air
- Details on exposure:
- Animal Exposure Methods:
Exposures were conducted in one cubic meter glass and stainless steel exposure chambers. Air for the chamber ventilation was supplied from a HVAC system separate from the general laboratory systems. This air was particulate filtered (99.9% + 0.3 µ) and controlled for temperature and humidity. Chamber airflow rate varied between 200 and 260 L/min depending on desired exposure concentrations.
Exposure chamber temperatures and relative humidity were recorded each day alter three and six hours of exposure. Table 1 presents the minimum and maximum and the mean temperature and relative humidity at the six hour measurement time for each group over the course of the study.
Exposure Atmosphere Generation Methods:
A vapor atmosphere of the test material was generated utilizing a counter-current vaporization system. This system operated as follows: The test material was pumped at a known and constant rate to the top of the bead column by a FMI® fluid metering pump or Sagee syringe drive.
Dry-compressed air passed up the bead column in a countercurrent manner relative to the liquid. Vaporization occurred on the bead column. The concentrated vapors were piped to the exposure chamber air inlet where dilution with chamber ventilation air reduced the concentration to the desired level. Table 2 summarizes the vapor generation system operating conditions. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Nominal exposure concentrations were calculated for all exposures. Actual exposure concentrations were measured by non-dispersive Infrared spectrophotometry utilizing a Wilks (MIRAN®) lA analyzer. The analyzer was calibrated by volumetric dilution of pure (97.5%) n-Butyl Mercaptan in saran gas bags. The calibration was checked once daily.
- Details on mating procedure:
- One female and one male animal of the same species and strain were placed together for mating. The occurrence of copulation was determined by daily inspection for a copulatory plug. The day evidence of mating was detected was designated day 0 of gestation and the female was returned to an individual cage.
- Duration of treatment / exposure:
- gestation days 6 - 16
- Frequency of treatment:
- 6 hour/day
- Duration of test:
- until GD17
- Dose / conc.:
- 10 ppm
- Remarks:
- 36.9 mg/m³ air (analytical) (group 2)
- Dose / conc.:
- 75 ppm
- Remarks:
- 250.9 mg/m³ air (analytical) (group 3)
- Dose / conc.:
- 150 ppm
- Remarks:
- 560.7 mg/m³ air (analytical)
- Dose / conc.:
- 10 ppm (analytical)
- Dose / conc.:
- 68 ppm (analytical)
- Dose / conc.:
- 152 ppm (analytical)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, sham-exposed
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
Prior to initiation of the treatment period all animals were observed twice daily for mortality and overt changes in appearance and behavior. All animals were observed daily for mortality and clinical signs of toxicity from gestation day 6 through sacrifice.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 15 and 17
FOOD CONSUMPTION: No
WATER CONSUMPTION : No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: uterus, abdominal and thoracic cavities and organs of the dams - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No data- Statistics:
- The male to female fetal sex distribution and the numbers of fetuses and litters with malformations were compared using the X2 test criterion with Yate's correction for 2X2 contingency tables and/or Fisher's exact probability test. The numbers of early and late resorptions, nonviable fetuses, and postimplantation loss were compared by the Mann-Whitney U test. The mean numbers of viable fetuses, total implantations, and corpora lutea, and mean fetal body weights were compared by analysis of variance (one way classification). Bartlett's test for homogeneity of variances, and the appropriate t test using Dunnett's multiple comparison tables were used to judge significance of differences. All statistical analyses compared the treatment group to the control group with the level of significance at p<0.05.
- Historical control data:
- Available in the report.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Emaciation, unkempt appearance, red or brown staining of the perivaginal region, lethargy, and/or staining of the hair was noted in mice at 68 and 152 ppm. These signs were exposure concentration related in respect of severity and/or incidence.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Seventeen treated mice died, eight at 68 ppm (0.25 mg/L) and nine at 152 ppm (0.56 mg/L) between days 11 and 17. Parturition was in progress in one mouse at 68 ppm at the time of death on day 15. A presumptive cause of death was not established for any descendent. All control and 10-ppm (0.04 mg/L) exposed mice survived.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A dose-related decrease in mean maternal body weight gain occurred during the treatment period (GD 6-17) and over the entire gestation period (GD 0-17) in all treatment groups when compared to the control. The adjusted mean maternal body weight gain over the entire gestation period was markedly reduced in group 4 when compared to the control group. The adjusted mean maternal body weight gain over the entire gestation period in groups 2 and 3 were slightly reduced when compared to the control group.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- In the treated groups, the mean relative kidney weights were slightly increased when compared to the control group. However, the mean absolute kidney weight in the treated groups was similar to the control group.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related trend in necropsy findings were observed. The kidneys were externally normal.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- There was an increase in mean post-implantation loss in groups 3 and 4 when compared to the control group and the mean value in the historical control data. This increase was statistically significant in group 4.
There was no biologically meaningful or statistically significant differences in the mean post-implantation loss in the low dose group.. - Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- Seven dams had resorptions only; one in group 3 and six in group 4.
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- There was no biologically meaningful or statistically significant differences in the number of early and late resorptions only in the low dose group..
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the reduced sample size the mean number of viable fetuses in group 4 could not be validly compared to the control group. A reduction in the mean number of viable fetuses, corresponding to the increase in the mean post-implantation loss, occurred in group 3 when compared to the control group; however this value was within the historical control data range.
There was no biologically meaningful or statistically significant differences in the number of viable fetuses in the low dose group. - Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In group 4, there was a decrease in the pregnancy rate and in mean number of total implantations when compared to the control group and the historical control data, but since ovulation and implantation in the mice in this study took place before the test material administration period, this decrease was not a treatment-related effect.
- Other effects:
- no effects observed
- Description (incidence and severity):
- There was no treatment-related trend in the mean number of corpora lutea in the treated groups when compared to the control group.
- Dose descriptor:
- NOAEC
- Effect level:
- >= 10 ppm (analytical)
- Basis for effect level:
- mortality
- Remarks on result:
- other: Equivalent to 36.9 mg/m³
- Abnormalities:
- not examined
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- There was no treatment-related trend in the mean fetal body weight in the treated groups when compared to the control group.
- Reduction in number of live offspring:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the reduced sample size the mean number of viable fetuses in group 4 could not be validly compared to the control group. A reduction in the mean number of viable fetuses, corresponding to the increase in the mean post-implantation loss, occurred in group 3 when compared to the control group; however this value was within the historical control data range.
There was no biologically meaningful or statistically significant differences in the number of viable fetuses in the low dose group. - Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- There was no treatment-related trend in the mean fetal sex distribution in the treated groups when compared to the control group.
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Cleft palate occurred in 8.3, 16.0 and 21.4% of the litters in groups 1 (control), 2 and 3, respectively. All of these values exceeded the range of the historical control data (0.0-5.6%). The malformations exencephaly, open eye and bend bones were noted in one fetus in one group 3 litter only; hydrocephaly was present in two fetuses in another litter in this group.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- There was no treatment related trend in the incidence of fetuses with the vertebral anomalies in litters in groups 2 and 3 when compared to the control.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was an increased incidence of litters with malformed fetuses in groups 2 and 3 when compared to the control group; however, the increase was not statistically significant.
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Because of the small sample size (only 30 fetuses from 3 litters) due to increased mortality, reduced pregnancy rate, and increased post-implantation loss, the incidence of malformations, genetic or developmental variations in treatment group 4 could not be validly compared to the control group. In this group a single instance of vertebral anomaly was the only malformation noted.
Cleft palate occurred in 8.3, 16.0 and 21.4% of the litters in groups 1 (control), 2 and 3, respectively. All of these values exceeded the range of the historical control data (0.0-5.6%). The malformations exencephaly, open eye and bend bones were noted in one fetus in one group 3 litter only; hydrocephaly was present in two fetuses in another litter in this group. There was no treatment related trend in the incidence of fetuses with the vertebral anomalies in litters in groups 2 and 3 when compared to the control. There was an increased incidence of litters with malformed fetuses in groups 2 and 3 when compared to the control group; however, the increase was not statistically significant.
The developmental or genetic variation noted in fetuses in the treatment groups did not occur in a treatment-related pattern and/or within the range of historical control data. - Dose descriptor:
- NOAEC
- Effect level:
- >= 68 ppm (analytical)
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Remarks on result:
- other: Equivalent to 250.9 mg/m³
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- In a developmental toxicity study in mice, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, mortality was observed at 1-butanethiol concentrations of 68 and 152 ppm (0.26 and 0.58 mg/L; measured); however, no fetal toxicity was observed in surviving animals. The NOAEC for maternal toxicity was 10 ppm (38 mg/m3) and ≥68 ppm (≥255 mg/m3) for developmental toxicity.
- Executive summary:
In a developmental toxicity study, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, groups of 25 pregnant CD-1 mice were whole body exposed to actual concentrations of 0, 10, 68, and 152 ppm 1-butanethiol, CAS 109-79-5 (0, 38, 255, and 570 mg/m3), 6 hours/day, on gestational days 6 to 16. Caesarean sections were performed on all surviving mice on gestational day 17. Throughout the study period, 17 pregnant mice died: 8 in 68 ppm group and 9 in 152 ppm group. Increased maternal toxicity characterised by a thin appearance, unkempt haircoat, very little movement and/or red or brown matter (presumably blood) in the vaginal region and a decrease in mean maternal body weight gain, was present in treatment groups. An increased post-implantation loss and early resorption occurred in 68 and 152 ppm groups. Due to the reduced sample size no valid comparison of fetal morphological observations in 152 ppm group could be made. An increase in the incidence of cleft palate was observed in the control group and 10 ppm and 68 ppm groups when compared to the historical control data, which was attributed to maternal stress. There were no biologically meaningful or statistically significant differences in the total incidence of malformations in fetuses in litters when compared to the appropriate control group. 1-Butanethiol did not produce teratogenic effects at exposure levels of 68 ppm or less in mice. At the 152 ppm exposure level the sample size was insufficient to evaluate possible teratogenic effects; however, no effects were observed in the available litters.
Overall, in pregnant mice, mortality was observed at concentrations of 68 and 152 ppm (0.26 and 0.58 mg/L); however, no fetal toxicity was observed in surviving animals. The NOAEC for maternal toxicity was 10 ppm (38 mg/m3) and ≥68 ppm (≥255 mg/m3) for developmental toxicity.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1982
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- limited information on animal husbandry and methods
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: The Charles River Breeding Laboratories Inc., Portage, Michigan, USA
- Age at study initiation: approximately 14 weeks old
- Weight at study initiation: 221-303 grams at the time of mating
- Housing: individually housed, except during mating, in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina® Certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 26 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: vapour
- Vehicle:
- air
- Details on exposure:
- Animal Exposure Methods:
Exposures were conducted in one cubic meter glass and stainless steel exposure chambers. Air for the chamber ventilation was supplied from a HVAC system separate from the general laboratory systems. This air was particulate filtered (99.9% + 0.3 µ) and controlled for temperature and humidity. Chamber airflow rate varied between 200 and 260 L/min depending on desired exposure concentrations.
Exposure chamber temperatures and relative humidity were recorded each day alter three and six hours of exposure. Table 1 presents the minimum and maximum and the mean temperature and relative humidity at the six hour measurement time for each group over the course of the study.
Exposure Atmosphere Generation Methods:
A vapor atmosphere of the test material was generated utilizing a counter-current vaporization system. This system operated as follows: The test material was pumped at a known and constant rate to the top of the bead column by a FMI® fluid metering pump or Sagee syringe drive.
Dry-compressed air passed up the bead column in a countercurrent manner relative to the liquid. Vaporization occurred on the bead column. The concentrated vapors were piped to the exposure chamber air inlet where dilution with chamber ventilation air reduced the concentration to the desired level. Table 2 summarizes the vapor generation system operating conditions. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Nominal exposure concentrations were calculated for all exposures. Actual exposure concentrations were measured by non-dispersive Infrared spectrophotometry utilizing a Wilks (MIRAN®) lA analyzer. The analyzer was calibrated by volumetric dilution of pure (97.5%) n-Butyl Mercaptan in saran gas bags. The calibration was checked once daily.
- Details on mating procedure:
- One female and one male animal of the same species and strain were placed together for mating. The occurrence of copulation was determined by daily inspection for a copulatory plug. The day evidence of mating was detected was designated day 0 of gestation and the female was returned to an individual cage.
- Duration of treatment / exposure:
- gestation days 6 - 19
- Frequency of treatment:
- 6 hour/day
- Duration of test:
- until GD20
- Dose / conc.:
- 10 ppm
- Remarks:
- 36.9 mg/m³ air (analytical) (group 2)
- Dose / conc.:
- 75 ppm
- Remarks:
- 250.9 mg/m³ air (analytical) (group 3)
- Dose / conc.:
- 150 ppm
- Remarks:
- 560.7 mg/m³ air (analytical)
- Dose / conc.:
- 10 ppm (analytical)
- Dose / conc.:
- 68 ppm (analytical)
- Dose / conc.:
- 152 ppm (analytical)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, sham-exposed
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
Prior to initiation of the treatment period all animals were observed twice daily for mortality and overt changes in appearance and behavior. All animals were observed daily for mortality and clinical signs of toxicity from gestation day 6 through sacrifice.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 16 and 20.
FOOD CONSUMPTION: No
WATER CONSUMPTION : No
POST-MORTEM EXAMINATIONS: Yes
On gestation day 20, all surviving dams were sacrificed by carbon dioxide inhalation. The abdominal and thoracic cavities and organs of the dams were examined for grossly evident morphological changes and the carcasses discarded. Uteri from females that appeared nongravid were placed in 10% ammonium sulfide solution for confirmation of pregnancy. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was externally sexed and individually numbered and tagged for identification.
- Soft tissue examinations: Yes
Approximately one-half of the fetuses were placed in Bouin's fixative for subsequent visceral examination by razor-blade sectioning as described by Wilson.
- Skeletal examinations: Yes
The remaining one-half of the fetuses were fixed in alcohol, macerated in potassium hydroxide and stained with Alizarin Red S by a method similar to that described by Dawson2 for subsequent skeletal examination.
- Head examinations: No - Statistics:
- The male to female fetal sex distribution and the numbers of fetuses and litters with malformations were compared using the X2 test criterion with Yate's correction for 2X2 contingency tables and/or Fisher's exact probability test. The numbers of early and late resorptions, nonviable fetuses, and postimplantation loss were compared by the Mann-Whitney U test. The mean numbers of viable fetuses, total implantations, and corpora lutea, and mean fetal body weights were compared by analysis of variance (one way classification). Bartlett's test for homogeneity of variances, and the appropriate t test using Dunnett's multiple comparison tables were used to judge significance of differences. All statistical analyses compared the treatment group to the control group with the level of significance at p<0.05.
- Historical control data:
- Available in the report.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight increase in the incidence of hair loss on the limbs was noted in group 4 when compared to the control group (group 1). Female #76523 and 76554 in groups 3 and 4 respectively, were dehydrated, Twenty-one rats had soft stool; 10, 8, 2 and 1 in the control, low (group 2), mid (group 3) and high (group 4) dose groups, respectively.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- Survival was 100% in all groups.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A very slight reduction in mean maternal body weight gain from gestation days 6-20 and over the entire gestation period (gestation days 0-20) was noted in the rats in the n-butyl Mercaptan treated groups 3 and 4 when compared to the control group. Similarly, the adjusted (dam weight on gestation day 20 minus gravid uterus weight) mean maternal body weight gain from gestation days 0-20 was reduced in these groups when compared to the control group. The mean maternal body weight gain during these intervals in group 2 was comparable to the control group. The adjusted mean maternal body weight gain from gestation days 0-20 was slightly reduced in this group when compared to the control group.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Both the mean absolute and relative kidney weights in the treated groups were comparable to the control group.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In female #76548 in group 4 the spleen was mottled, pitted and adhered to the connective tissue. In female #76547 in group 4 the left kidney was pitted.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In female #76548 in group 4, moderate focal capsular fibrosis was noted in spleen at histopathological examination.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- There were no biologically meaningful or statistically significant differences in the mean number of viable fetuses, postimplantation loss, total implantations, corpora lutea, or the fetal sex distribution in the treated groups when compared to the control group and the historical control data.
- Dose descriptor:
- NOAEC
- Effect level:
- >= 150 ppm (analytical)
- Basis for effect level:
- pre and post implantation loss
- other: No adverse effects observed.
- Remarks on result:
- other: Equivalent to 560 mg/m³
- Abnormalities:
- effects observed, non-treatment-related
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A statistically significant (p<0.05) increase in mean fetal body weight was present in group 3. This increase was within the range of the historical control data and was considered due to random occurrence.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Single instances of tail anomaly with associated small or no anal opening, scoliosis and/or pelvic anomaly were noted in one litter each in the groupa 3 and 4. The incidence of these malformations in the fetuses of groups 3 and 4 was within the range of occurrence in the historical control data and was not considered biologically meaningful.
There were no biologically meaningful trends in the occurrence of developmental and genetic variations in fetuses (or litters) in the treated groups when compared to the control group. - Dose descriptor:
- NOAEC
- Effect level:
- >= 150 ppm (analytical)
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Remarks on result:
- other: Equivalent to 560 mg/m³
- Abnormalities:
- no effects observed
- Developmental effects observed:
- not specified
- Conclusions:
- In a developmental toxicity study in rats, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, whole body inhalation exposure to the vapour concentrations of 0, 10, 68, and 152 ppm 1-butanethiol (0, 38, 255, and 570 mg/m3; measured) for 6 hours/day during gestation days 6 to 19, did not result in any treatment-related adverse systemic or developmental effects in maternal animals and their pups. The NOAEC for maternal and developmental toxicity was concluded to be ≥152 ppm (≥570 mg/m3) based on no treatment-related effects at the highest concentration tested.
- Executive summary:
In a developmental toxicity study, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, pregnant female rats (COBS CD; 25/group) were exposed (inhalation, whole body) to 1-butanethiol (n-butyl mercaptan) at target concentrations of 0, 10, 75 and 150 ppm (0, 36.9, 250.9 and 560.7 mg/m3 analytical, respectively) for 6 hours/day during gestation days (GD) 6-19. All rats survived until study termination. During the in-life portion of the study, a very slight decrease in mean maternal body weight gain was noted in the two highest exposure groups (75 and 150 ppm), and females from the highest exposure group (150 ppm) showed a slight increase (2/25 females) in the incidence of hair loss around the limbs as compared to control females. There was a statistically significant increase in mean fetal body weights in the group exposed at 75 ppm; however, because the increase was within the range of the historical control data, the finding was not considered to be treatment-related. Of the noted fetal malformations, all were within the range of occurrence in the historical control data and not considered to be biologically significant. In conclusion, there were no developmental/teratogenic effects or maternal toxicity in rats when administeredn-butyl mercaptanby whole body inhalation at or below the 150 ppm, the NOAEC for both maternal and fetal toxicity was 150 ppm (560.7 mg/m3 analytical).
Referenceopen allclose all
TABLE 4: Summary of Group Mean Maternal Body Weights
|
Control |
10 ppm |
100 ppm |
200 ppm |
Day of gestation |
Mean±S.D. |
Mean±S.D. |
Mean±S.D. |
Mean±S.D. |
0 |
29±2.39 |
29±2.1 |
29±2.6 |
29±2.0 |
6 |
31±2.6 |
31±2.3 |
32±2.7 |
30±4.0 |
9 |
33±2.6 |
33±2.7 |
34±2.6 |
33±3.2 |
12 |
38±3.0 |
38±2.9 |
39±3.6 |
38±3.0 |
15 |
44±3.5 |
45±3.3 |
46±4.4 |
46±3.4 |
17 |
51±4.0 |
51±3.6 |
52±5.6 |
52±4.2 |
17 (adjusted)a |
35±3.9 |
35±2.4 |
35±3.7 |
36±2.4 |
aDam body weight on gestation day 17 minus gravid uterus weight
TABLE 5: Summary of Group Mean Maternal and Fetal Observations at Cesarean Section
Group |
Control |
10 ppm |
100 ppm |
200 ppm |
||||||||
|
No. |
% |
S.D. |
No. |
% |
S.D. |
No. |
% |
S.D. |
No. |
% |
S.D |
Animals on study: |
25 |
- |
- |
24 |
- |
- |
25 |
- |
- |
25 |
- |
- |
Animals that were gravid: |
24 |
96.0 |
- |
24 |
96.0 |
- |
23 |
92.0 |
- |
21 |
84.0 |
- |
Animals that died: |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
Nongravid: |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Gravid: |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Animals that aborted/delivered: |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
Animals examined at Cesarean section: |
25 |
100.0 |
- |
25 |
100.0 |
- |
25 |
100.0 |
- |
25 |
100.0 |
- |
Nongravid: |
1 |
4.0 |
- |
1 |
4.0 |
- |
2 |
8.0 |
- |
4 |
16.0 |
- |
Gravid: |
24 |
96.0 |
- |
24 |
96.0 |
- |
23 |
92.0 |
- |
21 |
84.0 |
- |
Dams with resorptions only: |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
Dams with viable fetuses: |
24 |
100.0 |
- |
24 |
100.0 |
- |
23 |
100.0 |
- |
21 |
100.0 |
- |
Viable fetuses/dam: |
11.5 |
- |
2.34 |
11.1 |
- |
1.65 |
11.4 |
- |
2.19 |
11.3 |
- |
1.65 |
Postimplantation loss/dam: |
0.6 |
- |
0.88 |
0.9 |
- |
1.08 |
0.7 |
- |
0.76 |
0.7 |
- |
1.15 |
Total implantations/dam: |
12.1 |
- |
1.04 |
12.0 |
- |
2.00 |
12.1 |
- |
2.02 |
12.0 |
- |
1.80 |
Corpora lutea/dam: |
14.0 |
- |
2.10 |
13.9 |
- |
2.46 |
14.5 |
- |
3.51 |
14.6 |
- |
3.44 |
Fetal sex distribution Male: |
130 |
47.3 |
- |
128 |
47.9 |
- |
135 |
51.5 |
- |
110 |
46.2 |
- |
Female |
145 |
52.7 |
- |
139 |
52.1 |
- |
127 |
48.5 |
- |
128 |
53.8 |
- |
Mean fetal body weight (grams) |
0.88 |
- |
0.079 |
0.92 |
- |
0.094 |
0.92 |
- |
0.112 |
0.94 |
- |
0.092 |
Group mean preimplantation (%) |
- |
13.4 |
- |
- |
13.5 |
- |
- |
16.5 |
- |
- |
17.3 |
- |
Group mean postimplantation loss (%)b: |
- |
5.2 |
- |
- |
7.3 |
- |
- |
5.8 |
- |
- |
5.9 |
- |
aGroup mean preimplantation loss (%) =Total No. Corpora Lutea - Total No. Implantationsx 100
Total No. Corpora Lutea
bGroup mean postimplantation loss (%) =Total No. Implantations-Total No. Viable Fetuses x 100
Total No. Implantations
cValue does not include dams with regressing corpora lutea
*Significantly different from control group mean, p<0.05.
**Significantly different from control group mean, p<0.01.
- Not applicable
S.D.- Standard deviation
Table 6: Individual Maternal Liver Weight
Group |
Terminal bw (g) |
Liver weight (g) |
Relative liver weight (%) |
Control |
51±4.0 |
2.89±0.287 |
5.7±0.48 |
10 ppm |
51±3.6 |
2.97±0.249 |
5.9±0.46 |
100 ppm |
52±5.6 |
3.22±0.466 |
6.2±0.70 |
200 ppm |
52±4.2 |
3.58±0.385 |
6.9±0.57 |
TABLE 4: Summary of Group Mean Maternal Body Weights
Group |
Control |
10 ppm |
100 ppm |
200 ppm |
Day of gestation |
Mean±S.D. |
Mean±S.D. |
Mean±S.D. |
Mean±S.D. |
0 |
257±11.9 |
258±21.1 |
255±17.0 |
254±14.2 |
6 |
285±13.2 |
285±20.7 |
282±17.0 |
278±20.2 |
9 |
288±15.0 |
289±21.3 |
284±16.3 |
275±25.2 |
12 |
299±14.8 |
302±21.7 |
300±13.8 |
294±20.8 |
16 |
322±16.0 |
327±20.6 |
323±20.9 |
317±22.7 |
20 |
371±21.5 |
376±24.7 |
370±24.8 |
366±29.8 |
20 (adjusted)a |
298±16.6 |
300±18.5 |
294±15.2 |
295±18.4 |
aDam body weight on gestation day 20 minus gravid uterus weight
TABLE 5: Summary of Group Mean Maternal and Fetal Observations at Cesarean Section
Group |
Control |
10 ppm |
100 ppm |
200 ppm |
||||||||
|
No. |
% |
S.D. |
No. |
% |
S.D. |
No. |
% |
S.D. |
No. |
% |
S.D |
Animals on study: |
25 |
|
|
25 |
- |
|
25 |
|
- |
25 |
|
|
Animals that were gravid: |
23 |
92.0 |
|
24 |
96.0 |
- |
23 |
92.0 |
|
23 |
92.0 |
|
Animals that died: |
0 |
0.0 |
|
0 |
0.0 |
|
0 |
0.0 |
|
0 |
0.0 |
|
Nongravid: |
- |
- |
- |
- |
- |
- |
- |
- |
|
- |
- |
|
Gravid: |
- |
- |
- |
- |
- |
- |
- |
- |
|
- |
- |
|
Animals that aborted/delivered: |
0 |
0.0 |
|
0 |
0.0 |
- |
0 |
0.0 |
- |
0 |
0.0 |
- |
Animals examined at Cesarean section: |
25 |
100.0 |
|
25 |
100.0 |
- |
25 |
100.0 |
- |
25 |
100.0 |
- |
Nongravid: |
2 |
8.0 |
|
1 |
4.0 |
- |
2 |
8.0 |
- |
2 |
8.0 |
- |
Gravid: |
23 |
92.0 |
|
24 |
96.0 |
- |
23 |
92.0 |
- |
23 |
92.0 |
‑ |
Dams with resorptions only: |
0 |
0.0 |
|
0 |
0.0 |
- |
0 |
0.0 |
- |
1 |
4.4 |
‑ |
Dams with viable fetuses: |
23 |
100.0 |
|
24 |
100.0 |
- |
23 |
100.0 |
- |
22 |
95.7 |
‑ |
Viable fetuses/dam: |
14.0 |
- |
2.31 |
14.3 |
- |
1.81 |
14.1 |
- |
3.21 |
13.3 |
- |
3.66 |
Postimplantation loss/dam: |
0.6 |
- |
0.95 |
0.4 |
- |
0.50 |
0.5 |
- |
0.73 |
1.3 |
- |
2.95 |
Total implantations/dam: |
14.5 |
- |
1.88 |
14.8 |
- |
1.75 |
14.6 |
- |
3.37 |
14.7 |
- |
1.80 |
Corpora lutea/dam: |
16.4 |
- |
2.44 |
15.8 |
- |
1.80 |
16.5 |
- |
2.71 |
15.9 |
- |
1.17 |
Fetal sex distribution - Male: |
153 |
47.7 |
- |
167 |
48.5 |
- |
162 |
49.8 |
- |
140 |
45.6 |
‑ |
Female |
168 |
52.3 |
- |
177 |
51.5 |
- |
163 |
50.2 |
- |
167 |
54.4 |
- |
Mean fetal body weight (grams) |
3.3 |
- |
0.23 |
3.4* |
- |
0.21 |
3.5 |
- |
0.41 |
3.4 |
- |
0.22 |
Group mean preimplantation (%) |
- |
11.4 |
- |
- |
6.3 |
- |
- |
11.6 |
- |
- |
7,4c |
- |
Group mean postimplantation loss (%)b: |
- |
3.9 |
- |
- |
2.8 |
- |
- |
3.3 |
- |
- |
8.9 |
- |
aGroup mean preimplantation loss (%) =Total No. Corpora Lutea - Total No. Implantationsx 100
Total No. Corpora Lutea
bGroup mean postimplantation loss (%) =Total No. Implantations-Total No. Viable Fetuses x 100
Total No. Implantations
cValue does not include dams with regressing corpora lutea
*Significantly different from control group mean, p<0.05.
**Significantly different from control group mean, p<0.01.
- Not applicable
S.D.- Standard deviation
Table 6: Individual Maternal Organ Weight
Group |
Terminal bw (g) |
Kidney weight (g) |
Liver weight (g) |
Relative kidney weight (%) |
Relative liver weight (%) |
Control |
371±21.5 |
2.02±0.312 |
15.43±1.167 |
0.6±0.09 |
4.2±0.23 |
10 ppm |
376±24.7 |
2.02±0.349 |
15.45±1.612 |
0.5±0.08 |
4.1±0.34 |
100 ppm |
370±24.8 |
2.24±0.472 |
14.83±2.846 |
0.6±0.15 |
3.9±0.72 |
200 ppm |
366±29.8 |
2.08±0.152 |
15.4±1.67 |
0.6±0.12 |
4.2±0.27 |
Survival Data for Mice Dams and Fetuses
|
Control |
10 ppm NBM |
68 ppm NBM |
152 ppm NBM |
No. dams on study |
25 |
25 |
25 |
25 |
No. dams dying on study |
- |
- |
8 |
9 |
No. gravid dams dying on study |
- |
- |
8 |
8 |
No. surviving dams |
|
|
|
|
Nongravid |
1 |
- |
2 |
7 |
Gravid |
24 |
25 |
15 |
9 |
Total corpora lutea |
335 |
342 |
194 |
41 |
Corpora lutea/gravid dam |
14.0 |
13.7 |
12.9 |
13.7 |
Total implants |
290 |
303 |
180 |
90 |
Implants/gravid dam |
12.1 |
12.1 |
12.0 |
10.0 |
Number with resportions only |
0 |
0 |
1 |
6 |
Total viable fetuses |
275 |
275 |
148 |
30 |
Viable fetuses/gravid dam |
11.5 |
11.0 |
9.9 |
3.3a |
Total early resorptions |
5 |
11 |
25 |
59 |
Early resorptions/gravid dam |
0.2 |
0.4 |
1.7* |
6.6** |
Postimplantation loss/gravid dam |
0.6 |
1.1 |
2.1 |
6.7** |
aSix dams showed early regressing resorption sites and no viable fetuses.
*Significantly different from control p<0.05
**Significantly different from control p<0.01
Summary of the Incidence of Fetal External, soft tissue, and Skeletal Malformations
Malformations observed |
Control |
10 ppm NBM |
68 ppm NBM |
152 ppm NBM |
||||
|
No. fetuses |
% |
No. fetuses |
% |
No. fetuses |
% |
No. fetuses |
% |
External malformations |
|
|
|
|
|
|
|
|
Cleft Palate |
2 |
0.7 |
4 |
1.5 |
5 |
3.4 |
0 |
0 |
Open Eye |
0 |
0 |
0 |
0 |
1 |
0.7 |
0 |
0 |
Exencephaly |
0 |
0 |
0 |
0 |
1 |
0.7 |
0 |
0 |
Soft tissue malformations |
|
|
|
|
|
|
|
|
Hydrocephaly |
0 |
0 |
0 |
0 |
2 |
2.7 |
0 |
0 |
Skeletal malformations |
|
|
|
|
|
|
|
|
Vertebral anomaly |
5 |
3.6 |
7 |
5.1 |
5 |
6.8 |
1 |
6.3 |
Bent bones |
0 |
0 |
0 |
0 |
1 |
1.4 |
0 |
0 |
Total fetuses/% with malformations |
7 |
2.5 |
11 |
4.0 |
12* |
8.1 |
1 |
3.3 |
* significantly different from control p</= 0.5
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subchronic
- Species:
- rat
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
There are no developmental toxicity data for n-propyl mercaptan, (1-propanethiol; CAS 107-03-9), therefore data were read-across from the structurally analogous substances tert-butyl mercaptan (2-methylpropane-2-thiol; CAS 75-66-1) and n-butyl mercaptan (1-butanethiol; CAS 109-79-5). 1-Propanethiol (NPM, target), 1-butanethiol (source) and 2-methylpropane-2-thiol (source) all contain a thiol (-SH) functional group with a branched or linear aliphatic carbon chain. See attachment to Section 13 for justification of read-across.
In a combined repeated dose/reproductive/developmental toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP, groups of male and female Sprague-Dawley rats (12-17/sex/dose) were administered 2-methylpropane-2-thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated.
There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.
This study was classified as reliable with restriction because although it is a GLP guideline study, a study report in English was not available for data verification. However, this study is peer reviewed and considered sufficient for this endpoint.
In a rat developmental toxicity / teratogenicity study (Ulrich, 1982b), conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, pregnant female Sprague-Dawley rats (COBS CD; 25/concentration) were exposed to analytical concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm) of 2-methylpropane-2-thiol via whole-body inhalation 6 hrs/day during gestational days 6-19. All rats survived until study termination. During the in-life portion of the study, there was an increase in the number of rats with hair loss in the treated groups when compared to the control group; however, there were no other signs of maternal toxicity. At necropsy, there were no biologically relevant or statistically significant differences in the mean number of viable fetuses, total implantations, corpora lutea, or fetal sex distribution in the exposed groups as compared to controls. Fetal evaluations did not reveal biologically relevant or statistically significant differences in malformations among the dosed animals as compared to the controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when 2-methylpropane-2-thiol was administered by whole-body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and fetal NOAEC was ≥ 195 ppm, equivalent to 721 mg/m³.
In a similar key mouse developmental toxicity / teratogenicity study (Ulrich, 1982b), conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, pregnant female mice (CD-1; 25/group) were exposed to analytical concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm) of 2-methylpropane-2-thiol via whole-body inhalation 6 hrs/day during gestational days 6-16. All animals survived to scheduled termination. There were no statistically significant differences between the dosed animals and controls with respect to maternal endpoints. Fetal malformations were observed in mice exposed to 99 ppm (litter incidence, 47.8 %) and 195 ppm (litter incidence, 28.6%) when compared to the control group (litter incidence, 16.7%). The particular malformation noted (i. e., vertebral anomaly), however, did not increase in a dose-related pattern and was in the range of historical control data. There were no additional statistically significant differences in treated fetuses when compared to controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when 2-methylpropane-2-thiol was administered by whole-body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and fetal NOAEC was ≥ 195 ppm, equivalent to 721 mg/m³.
In a developmental toxicity study, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, pregnant female rats (COBS CD; 25/group) were exposed (inhalation, whole body) to 1-butanethiol at target concentrations of 0, 10, 75 and 150 ppm (0, 36.9, 250.9 and 560.7 mg/m3 analytical, respectively) for 6 hours/day during gestation days (GD) 6-19 (Ulrich, 1982b; Thomas, 1987). All rats survived until study termination. During the in-life portion of the study, a very slight decrease in mean maternal body weight gain was noted in the two highest exposure groups (75 and 150 ppm), and females from the highest exposure group (150 ppm) showed a slight increase (2/25 females) in the incidence of hair loss around the limbs as compared to control females. There was a statistically significant increase in mean fetal body weights in the group exposed at 75 ppm; however, because the increase was within the range of the historical control data, the finding was not considered to be treatment-related. Of the noted fetal malformations, all were within the range of occurrence in the historical control data and not considered to be biologically significant. In conclusion, there were no developmental/teratogenic effects or maternal toxicity in rats when administered n-butyl mercaptan by whole body inhalation at or below the 150 ppm, the NOAEC for both maternal and fetal toxicity was 150 ppm (560.7 mg/m3 analytical).
In a developmental toxicity study, conducted according to a protocol similar to OECD Test Guideline 414 and in compliance with GLP, groups of 25 pregnant CD-1 mice were whole body exposed to actual concentrations of 0, 10, 68, and 152 ppm 1-butanethiol (0, 38, 255, and 570 mg/m3), 6 hours/day, on gestational days 6 to 16. Caesarean sections were performed on all surviving mice on gestational day 17 (Ulrich, 1982b; Thomas, 1987). Throughout the study period, 17 pregnant mice died: 8 in 68 ppm group and 9 in 152 ppm group. Increased maternal toxicity characterised by a thin appearance, unkempt haircoat, very little movement and/or red or brown matter (presumably blood) in the vaginal region and a decrease in mean maternal body weight gain, was present in treatment groups. An increased post-implantation loss and early resorption occurred in 68 and 152 ppm groups. Due to the reduced sample size no valid comparison of fetal morphological observations in 152 ppm group could be made. An increase in the incidence of cleft palate was observed in the control group and 10 ppm and 68 ppm groups when compared to the historical control data, which was attributed to maternal stress. There were no biologically meaningful or statistically significant differences in the total incidence of malformations in fetuses in litters when compared to the appropriate control group. 1-Butanethiol did not produce teratogenic effects at exposure levels of 68 ppm or less in mice. At the 152 ppm exposure level the sample size was insufficient to evaluate possible teratogenic effects; however, no effects were observed in the available litters. Overall, in pregnant mice, mortality was observed at concentrations of 68 and 152 ppm (0.26 and 0.58 mg/L); however, no fetal toxicity was observed in surviving animals. The NOAEC for maternal toxicity was 10 ppm (38 mg/m3) and ≥68 ppm (≥255 mg/m3) for developmental toxicity.
Justification for classification or non-classification
Based on the available read-across data for tert-butyl mercaptan (2-methylpropane-2-thiol; CAS 75-66-1) and n-butyl mercaptan (1-butanethiol; CAS 109-79-5), no classification for reproductive or developmental toxicity is required for the registered substance, n-propyl mercaptan, (propane-1-thiol; CAS 107-03-9), according to Regulation (EC) No 1272/2008.
Additional information
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