Hydrocarbons, C10, aromatics, <1% naphthalene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There is no fertility/reproductive toxicity data available for Hydrocarbons, C10, aromatics, <1% naphthalene. However, data is available for structural analogues, Hydrocarbons, C9, aromatics, and N-butyl benzene and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

C9 Aromatic hydrocarbons: Inhalation NOAEC = 1500 ppm (7500 mg/m³)

N-butylbenzene: Oral NOAEL >=300 mg/Kg bw/day.

Additionally, in order to comply with standard information requirements for Annex X substances, an OECD 443 test is proposed for structural analogue Hydrocarbons, C11-C15, aromatics, <1% Naphthalene (EC# 922 -153 -0). The testing proposal for the same has been presented in the lead registrant dossier for this substance already submitted to ECHA. This study will be conducted subsequent to ECHA’s approval and this endpoint will be updated upon completion of the above study.  

Link to relevant study records

Reference

Reference 1

Endpoint:

three-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented publication which meets basic scientific principles.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Principles of method if other than guideline:

30 rats of each sex (F0 generation) were exposed via inhalation to 100, 500, or 1500 ppm of high flash aromatic naphtha for 6 hrs/day, 5 days/week for 10 weeks. Rats were then mated, and females confirmed mated were then exposed for 6 hrs/day during gestation days 0 to 20. Dams were not exposed during delivery, but exposure was reinitiated on postnatal day 5 and continued through postnatal day 21 (weaning). This F1 generation was then exposed for 10 weeks starting at 5 to 7 weeks of age, then mated to produce the F2 generation. The F2 generation was treated similarly to the F1 generation, except they were exposed immediately after weaning to produce the F3 generation. Fertility indices were calculated for all parental generations (F0, F1, and F2), female mating index, female conception index, female gestation index, male fertility index, cohabitation time, and litter size at birth. The gestational survival and postnatal survival indexes of the F1, F2, and F3 generations were also calculated.

GLP compliance:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI
- Age at study initiation:(P) 6 x wks; (F1) 5-7 x wks; (F2) 22 days
- Housing: Individually housed in wire mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow No. 5002 ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2-3 weeks


ENVIRONMENTAL CONDITIONS
Animal husbandry followed standards by the US Department of Health, Education, and Welfare (1985)

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Details on exposure:

- Exposure apparatus: 16 m glass and steel chambers.
- Method of holding animals in test chamber: cages
- Source and rate of air: Air was provided by a separate HVAC system.
- Method of conditioning air: Air was filtered for particulates and temperature and humidity controlled.
- System of generating particulates/aerosols: Test atmosphere was generated by heating nitrogen to 200°C by passing it through a 1 l stainless steel cylinder with a 1500 W band heater. The nitrogen then passed through a glass column 7.6 cm diameter and 30 cm long packed with glass beads. Test material was delivered by a metering pump into Teflon tubing, to the bottom of the column. The liquid test substance vaporized as it went up the column with the nitrogen. The vapor then went into the test chambers where dilution with the chamber ventilation air produced the desired concentrations.
- Temperature, humidity, pressure in air chamber: Air flow rate, temperature and relative humidity were monitored every half-hour during exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: Measurements made hourly using gas-phase IR.
- Samples taken from breathing zone: yes

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: sperm-positive vaginal smear referred to as day 0 of pregnancy

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentration of the test material in the test chambers was determined by GC analysis.

Frequency of treatment:

Both males and females were exposed 6 hours per day 5 days/ week for 10 weeks before mating. After mating, females were exposed 6 hours/day, 7 days/week from Gestation Day (GD) 0 to GD 20. Dams were then removed to nesting boxes to deliver. Dams were again exposed from postnatal day (LD) 5 until weaning on LD 21.

Details on study schedule:

- F1 parental animals not mated until 10 weeks after selected from the F1 litters.
- Selection of parents from F1 generation one week after weaning.
- Age at mating of the mated animals in the study: 15-17 weeks

Remarks:

Doses / Concentrations:
0, 100, 500, 1500 ppm
Basis:
nominal conc.
0, 500, 2500, 7500 mg/m3

Remarks:

Doses / Concentrations:
0, 103, 495, 1480 ppm
Basis:
analytical conc.
0, 515, 2475, 7400 mg/m3

No. of animals per sex per dose:

30, except for F2 generation in which 40 animals/sex/dose were selected. In the 1500 ppm F2 group all surviving animals were mated.

Control animals:

yes, concurrent no treatment

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily for viability and overt toxicity.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly until confirmation of mating; females weighed on GD 0, 7, 14, 21, and LD 0, 7, 14, 21

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, weekly except during mating, gestation, and lactation
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

Litter observations:

STANDARDISATION OF LITTERS
Litters were culled by random selection to 8 pups on LD4.


PARAMETERS EXAMINED
The following parameters were examined in F1/F2/F3 offspring:
Number of pups, stillbirths, live births, presence of gross anomalies was examined as soon as possible after delivery. Pups weighed individually on LD 0, 4, 7, 14. On LD21 all pups were counted, sexed, and weighed.


GROSS EXAMINATION OF DEAD PUPS:
Yes, culled pups and any pups that died were necropsied for gross abnormalities.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals were necropsied at end of mating period.
- Maternal animals: All surviving animals were necropsied following weaning.

HISTOPATHOLOGY
In control and high dose group the epididymus, lung, ovary, pituitary, prostate, seminal vesicle, testis, uterus, vagina, lymph nodes were examined. Masses and gross lesions were examined from all groups.

ORGAN WEIGHTS
Epididymus, lung, ovary, testis, prostate/seminal vesicle, uterus/vagina

Postmortem examinations (offspring):

SACRIFICE
- The F1/F2 offspring not selected as parental animals were sacrificed at 8 days of age. F3 offspring were sacrificed at LD21.



GROSS NECROPSY
Culled pups and any pups that died were necropsied for gross abnormalities.


HISTOPATHOLOGY / ORGAN WEIGTHS
F1/F2 offspring were examined the same as parental animals.

Statistics:

Fertility indices and female/male ratio was analysed using Chi-square test criterion with Yate's correction. Proportions of litters with malformations were compared using Fisher's exact probability test. Proportions of resorbed fetuses, implantation losses, and pup survival were compared using Mann-Whitney U test. Mean number of liveborn pups/litter and pup weight were compared using analysis of variance and appropriate t-tests. Other parameters were compared using analysis of variance, appropriate t-test, and Dunnett's multiple comparison tables.

Reproductive indices:

female mating index: number pregnant females/number of females mated
female conception index: number females delivering live litter/number pregnant females
female gestational index: number of females delivering live litter/number females delivering a litter
male fertility index: number of fertile males/number of males mated
Cohabitation time: average number male/female cohabitation days
litter size at birth

Offspring viability indices:

Gestational survival index: number pups live born/number of pups born
Postnatal survival index (4-day): number pups alive at LD4/number of liveborn pups
Postnatal survival index (21-day): number pups alive at LD21/number of liveborn pups

Clinical signs:

effects observed, treatment-related

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:

not examined

Histopathological findings: non-neoplastic:

not examined

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
All males survived with minimal signs of toxicity. 7 females in the 1500 ppm group died.


BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Body weight gain of P males and females was significantly reduced in the 500 ppm and 1500 ppm groups. Food consumption was reduced in the 1500 ppm group in the first week.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
Length of time for mating was increased, but not significantly.

GROSS PATHOLOGY (PARENTAL ANIMALS)
There were no significant pathological findings in the reproductive organs in any group of animals in any generation in any dose group.

F1
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
In the 1500 ppm group ataxia and reduced motor activity was observed. 6 females in this group also died.


BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Mean body weights of 1500 ppm group, and males in the 500 ppm group were significantly less than control groups. Food consumption was normal.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
Length of time for mating was increased, but not significantly. Male fertility was reduced, however, as this effect was not seen in the first and third generations, this is not considered to be exposure related.

F2
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
Most of the animals (36/40 males and 34/40 females) in the high exposure group (1500 ppm) died within the first week. All other animals survived.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Body weight gain of high exposure males and females were severely below control (up to 40%). Body weights in the 500 ppm and 100 ppm exposure groups were mildly depressed (10%). Food consumption was similar for all groups.

Key result

Dose descriptor:

NOAEC

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

other: 7500 mg/m3; When maternal exposure ceased before gestation day 20, there were no negative effects on fertility or on the offspring.

Remarks on result:

other: Generation: offspring of all generations (migrated information)

Key result

Dose descriptor:

LOAEC

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

other: 7500 mg/m3; Maternal lethality, and reduced body weight in offspring were noted if maternal exposure was continued beyond GD20 and until delivery. ("prolonged exposure" group in Table).

Remarks on result:

other: Generation: offspring of all generations (migrated information)

Clinical signs:

not examined

Mortality / viability:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

F1
VIABILITY (OFFSPRING)
No significant differences through the lactational period.

BODY WEIGHT (OFFSPRING)
No significant difference in body weights or birth weight, except for pups from the 1500 ppm group at LD7 through weaning.

F2
VIABILITY (OFFSPRING)
Mean birth weight in the 1500 ppm group was reduced, but not significantly. The mean number of live offspring/litter, and number liveborn/number delivered was significantly reduced in this group. This was most likely due to litters from dams which had not been confirmed to have mated. These unconfirmed dams were exposed until delivery, whereas the other dams were not exposed after GD20. The birth weight from these litters were not significantly reduced.

BODY WEIGHT (OFFSPRING)
Mean body weights in the 1500 ppm group after LD7 were significantly reduced.

F3
VIABILITY (OFFSPRING)
There were no apparent effects on mating, fertility, mean number of live births, and survival through lactation period.

BODY WEIGHT (OFFSPRING)
Mean weight of the offspring in the high exposure group was significantly reduced at birth. This may have been the result of the small sizes of the dams. If maternal exposure was ceased, the body weight gain became normal, but if reinitiated, the body weights were again reduced.

Key result

Dose descriptor:

NOAEC

Generation:

F2

Effect level:

1 500 other: 1500 ppm (7500 mg/m3)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Reproductive Toxicity

Key result

Dose descriptor:

LOAEC

Generation:

F2

Effect level:

1 500 other: ppm (7500 mg/m3)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Reproductive Toxicity

Key result

Reproductive effects observed:

no

Significant Effects of Exposure to High Flash Aromatic Naptha (SD)

Male Fertility Index	F0	F1	F2
0	86.7 (30)	89.7 (30)	93.3 (30)
100	96.7 (30)	86.7 (30)	83.3 (30)
500	83.3 (30)	93.3 (30)	80.0 (30)
1500	84.6 (26)	64.3 (28)	100 (4)
Litter Size at Birth	F0	F1	F2
0	12.1 ± 3.4	12.4 ± 2.0	12.6 ± 2.7
100	12.9 ± 1.5	11.1 ± 2.9	11.8 ± 2.3
500	12.2 ± 3.1	11.7 ± 3.0	11.4 ± 2.1
1500	11.3 ± 3.0	8.7 ± 4.3	12.2 ± 1.3
Gestational Survival Index	F1	F2	F3
0	95.9 (366)	97.4 (383)	97.7 (361)
100	97.9 (382)	95.4 (280)	98.2 (335)
500	94.9 (333)	91.6 (371)	98.5 (325)
1500	92.8 (279)	85.1 (215)	100 (73)

Gestational Survival Index Among Rats in the F2 Generation

Concentration	Total % (SD)	Prolonged Exposure (%) SD	Exposure Stopped on GD20 (%) SD
0	97.4 (383)	91.9 (74)	98.7 (309)
100	95.4 (280)	91.7 (96)	97.2 (184)
500	91.6 (371)	30.8 (13)	93.8 (358)
1500	85.1 (215)	63.0 (54)	92.5 (161)

Body Weights of Pups

Concentration (ppm)	F1	F2	F3
	Day 0
0	6.1± 0.5	6.0 ±0.5	6.0 ±0.5
100	6.2 ±0.5	6.1 ±0.5	6.0 ±0.4
500	6.5 ±0.6	6.0± 0.5	6.1 ±0.6
1500	6.1± 1.0	5.7 ±0.7	5.7 ±0.2
	Day 4
0	9.7 ±0.9	9.5 ±1.4	9.7 ±1.1
100	9.8 ±0.6	10.0± 1.2	10.0 ±0.7
500	10.1 ±1.0	9.9 ±1.0	9.8 ±1.0
1500	9.2 ±1.3	9.3 ±1.0	9.2 ±0.6
	Day 7
0	13.7 ±1.3	13.3 ±1.8	14.0±2.0
100	13.2 ±1.1	13.3 ±1.6	14.1 ±1.2
500	14.0 ±1.7	13.5 ±1.4	13.4 ±1.5
1500	12.0 ±1.8	11.7 ±1.3	12.0 ±1.0
	Day 14
0	24.9± 2.7	24.3 ±2.5	26.2± 4.0
100	23.2 ±1.8	23.5 ±2.8	25.6 ±1.9
500	23.9 ±2.4	23.7 ±2.7	23.2 ±2.7
1500	19.6 ±2.7	19.3 ±1.8	20.8 ±1.3
	Day 21 Male Body Weights
0	39.5 ±5.1	40.9 ±5.5	42.9 ±7.6
100	37.2 ±5.9	39.3 ±5.5	42.7 ±3.8
500	40.0 ±4.9	39.7 ±5.6	38.7± 5.1
1500	29.9 ±3.6	30.4 ±4.2	32.8 ±3.0
	Day 21 Female Body Weights
0	38.0 ±5.0	39.6 ±5.1	41.4 ±6.2
100	35.7 ±5.7	37.9 ±4.8	41.2 ±3.6
500	38.0 ±5.0	38.6 ±5.5	37.2 ±4.8
1500	29.4 ±4.3	29.1 ±4.2	31.8 ±3.6

Conclusions:

The test substance NOAEC for fertility effects is 1500 ppm (7500 mg/m3) for male and female rats.

Executive summary:

This study was conducted to determine the reproductive toxicity of high flash aromatic naphtha. 30 rats of each sex (F0 generation) were exposed via inhalation to 100, 500, or 1500 ppm (0, 500, 2500, 7500 mg/m3) of high flash aromatic naphtha for 6 hrs/day, 5 days/week for 10 weeks. Rats were then mated, and females confirmed mated were then exposed for 6 hrs/day during gestation days 0 to 20. Dams were not exposed during delivery, but exposure was reinitiated on postnatal day 5 and continued through postnatal day 21 (weaning). This F1 generation was then exposed for 10 weeks starting at 5 to 7 weeks of age, then mated to produce the F2 generation. The F2 generation was treated similarly to the F1 generation, except they were exposed immediately after weaning to produce the F3 generation. Under these conditions, reduced survival and body weight gains were observed in the offspring of the high exposure group. Although this was evidence of a toxic effect at the highest dose tested, there were no reproductive effects.

 

Fertility indices were calculated for all parental generations (F0, F1, and F2), female mating index, female conception index, female gestation index, male fertility index, cohabitation time, and litter size at birth. The gestational survival and postnatal survival indexes of the F1, F2, and F3 generations were also calculated. The results of the fertility study show no exposure related adverse effects to fertility in either male or female rats, therefore the NOAEC for fertility is 1500 ppm (7500 mg/m3) for high flash aromatic naphtha.

Reference 2

Endpoint:

two-generation reproductive toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: non-GLP. Source of data is from peer reviewed literature.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reproductive effects observed:

not specified

Executive summary:

This data is being read across from the source study that tested N-butyl benzene based on analogue read across.

N-butylbenzene (n-BB) was administered orally by gavage at dose levels of 0, 30, 100, and 300 mg/kg/day to groups of Crj: CD (SD) IGS rats (24 males and 24 females per group) over 2 generations, and the effects on fertility of the parental animals and development/growth of the offspring were investigated.In the F0 and F1 parental animals, n-BB at the doses of 30 mg/kg/day and above increased the liver weights, and the doses of 100 and 300 mg/kg/day increased the kidney weights and caused histopathological changes in the liver and kidney. Moreover, the dose of 300 mg/kg/day also increase adrenal gland weights and there was a tendency for inhibition of body weight gain. With respect to effects on fertility, no significant findings were noted in the F0 parental males and females. Furthermore, it was concluded that n-BB did not induce serious reproductive toxicity in the F1 parental animals and no effects on the endocrine system were observed.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Species:

rat

Quality of whole database:

One supporting read across oral study from a structural analogue available for assessment.

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

7 500 mg/m³

Species:

rat

Quality of whole database:

One key read across inhalation toxicity study from a structural analogue available for assessment.

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There is no fertility/reproductive toxicity data available for Hydrocarbons, C10, aromatics, <1% naphthalene. However, data is available for structural analogues, Hydrocarbons, C9, aromatics, and N-butyl benzene and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Inhalation

C9 Aromatic hydrocarbons

The read-across material, C9 Aromatic hydrocarbons, was examined for toxicity in a three-generation reproductive toxicity study (McKee et al., 1990). 30 rats of each sex (F0 generation) were exposed via inhalation to 100, 500, or 1500 ppm of high flash aromatic naphtha for 6 hrs/day, 5 days/week for 10 weeks. Rats were then mated, and females confirmed mated were then exposed for 6 hrs/day during gestation days 0 to 20. Dams were not exposed during delivery, but exposure was reinitiated on postnatal day 5 and continued through postnatal day 21 (weaning). This F1 generation was then exposed for 10 weeks starting at 5 to 7 weeks of age, then mated to produce the F2 generation. The F2 generation was treated similarly to the F1 generation, except they were exposed immediately after weaning to produce the F3 generation. Under these conditions, reduced survival and body weight gains were observed in the offspring of the high exposure group. Although this was evidence of a toxic effect at the highest dose tested, there were no reproductive effects. The NOAEC was determined to be >=1500 ppm mg/kg bw/day for males and females. Based on this study, Hydrocarbons, C10, aromatics, >1% naphthalene is not expected to be a reproductive toxicant.

 

Oral

N-butyl benzene

N-butylbenzene, a C10 aromatic hydrocarbon, was examined for toxicity in a two-generation reproductive toxicity study (Izumi, 2005). N-butylbenzene was administered by oral gavage at dose levels of 0, 30, 100, and 300 mg/kg/day to groups of Crj: CD (SD) IGS rats (24 males and 24 females per group) over 2 generations, and the effects on fertility of the parental animals and development/growth of the offspring were investigated. It was concluded that n- butylbenzene did not induce reproductive toxicity in the F1 parental animals and no effects on the endocrine system were observed. Therefore, the NOAEL was determined to be >=300 mg/Kg bw/day. Based on this study, Hydrocarbons, C10, aromatics, >1% naphthalene is not expected to be a reproductive toxicant.

Effects on developmental toxicity

Description of key information

There is no developmental toxicity data available for Hydrocarbons, C10, aromatics, <1% naphthalene. However, data is available for structural analogues, Hydrocarbons, C9 Aromatics and Isopropyl benzene and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Hydrocarbons, C9, aromatics: inhalation NOAEC (Mouse): 100 ppm

Isopropyl benzene: inhalation NOAEC (Rat): >1200 ppm

Isopropyl benzene: inhalation NOAEC (Rabbit): >2300 ppm

Additionally, in order to comply with standard information requirements for Annex X substances, OECD 414 tests (Rats and Rabbits) are proposed for structural analogue Hydrocarbons, C11-C15, aromatics, <1% Naphthalene (EC# 922-153-0). The testing proposals for the same have been presented in the lead registrant dossiers for this substance already submitted to ECHA. These studies will be conducted subsequent to ECHA’s approval and this endpoint will be updated upon completion of the above studies.   

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

Study duration:

subacute

Species:

mouse

Quality of whole database:

Three key/WOE read across developmental toxicity studies (Rat and Rabbit) from structural analogues available for assessment.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

There is no developmental toxicity data available for Hydrocarbons, C10, aromatics, <1% naphthalene. However, data is available for structural analogues, Hydrocarbons, C9, aromatics and Isopropyl benzene and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Hydrocarbons, C9, aromatics

A key study (McKee et al., 1990) was conducted to determine the developmental toxicity of high flash aromatic naphtha. Groups of 30 pregnant female mice were exposed via inhalation to 100, 500, or 1500 ppm of high flash aromatic naphtha for 6 hrs per day during gestation days 6 -15. The mice were sacrificed on gestation day 18, and examined for a variety of fetal developmental parameters including number of viable and nonviable fetuses, number of resorptions, total implantations, and number of corpea lutea. Animals were also examined for maternal toxicity signs including body weight, and changes in appearance and behaviour. There was a statistically significant reduction in body weight gain in dams and reduced mean body weight for fetuses in the 500 ppm exposure group. Therefore, the maternal and developmental toxicity NOAEC = 100 ppm. The maternal toxicity LOAEC was 500 ppm based on significant reduction in weight gain for the dams. The development toxicity LOAEC was 500 ppm based on significant reduction in weight gain likely caused by the significant reduction in maternal body weight.

Isopropyl benzene

A study was conducted to determine the developmental toxicity of isopropyl benzene, a C9 aromatic substance and a component of complex C9 aromatic hydrocarbon solvents (Darmer et al., 1997). Groups of 25 pregnant female rats were exposed via inhalation to 100, 500, or 1200 ppm of isopropyl benzene 6 hrs per day during gestation days 6 -15. Rats were sacrificed on gestation day 21 and both dams and fetuses were examined for adverse effects. Aside from a statistically significant reduction in maternal body weight gain (1200 ppm) and food consumption (500 and 1200 ppm), no other adverse treatment-related effects were found. Maternal NOAEC was determined to be 500 ppm on the basis of reduced maternal body weight gain. Fetal NOAEC was determined to be greater than 1200 ppm.

A second study was conducted to determine the developmental toxicity of isopropyl benzene, a C9 aromatic substance and a component of complex C9 aromatic hydrocarbon solvents (Darmer et al., 1997). Groups of 15 pregnant female rabbits were exposed via inhalation to 500, 1200, or 2300 ppm of isopropyl benzene 6 hrs per day during gestation days 6 -18. Rabbits were sacrificed on gestation day 29 and both dams and fetuses were examined for adverse effects. Aside from a statistically significant reduction in maternal body weight gain (2300 ppm) and food consumption (500 and 1200 ppm), no other adverse treatment-related effects were found. Maternal NOAEC was determined to be 1200 ppm on the basis of reduced maternal body weight gain. Fetal NOAEC was determined to be greater than 2300 ppm.

Justification for classification or non-classification

Based on the results from read across studies, Hydrocarbons, C10, aromatics, <1% naphthalene does not warrant classification as a reproductive or developmental toxicant under Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP). However, further tests (OECD 443 and OECD 414 (rodent and 2nd species)) are proposed on a structural analogue and will be conducted subsequent to ECHA's approval of the same. This endpoint will be updated upon completion of the above studies subject to ECHA's approval.