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Registration Dossier
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EC number: 250-264-8 | CAS number: 30618-84-9
- 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
Description of key information
The subacute oral NOAEL for GMT is 50 mg/kg bw/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11-July-2006 - 30-Nov-2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP and guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Remarks:
- Dept. of Health, UK
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent.
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 280 - 379 g; Females: 192 - 260 g
- Housing: All animals were housed in groups of five in polypropylene cages with stainless steel grid floors and tops, suspended over polypropylene trays lined with absorbent paper. During the mating phase, animals were transferred to similar cages on a one male: one female basis.
Following evidence of successful mating, the males were returned to their original cages. Mated females were housed individually during gestation and lactation, in polypropylene cages with solid floors and stainless steel lids, furnished with softwood flakes (Datesand Ltd. Cheshire, UK).
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 28 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15 % relative humidity
- Air changes (per hr): 15 x / h
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- - The test material was administered by gavage to three groups each of ten male and ten female rats, for up to fifty-four consecutive days, at dose levels of 15, 50 and 150 mg/kg/day.
- A control group of ten males and ten females was dosed with vehicle alone (Deoxygenated and demineralised water).
- Two recovery groups, each of five males and five females, were treated with the high dose (150 mg/kg/day) or the vehicle alone for
forty-three consecutive days and then maintained without treatment for a further fourteen days. - Duration of treatment / exposure:
- - for up to fifty-five days
- Frequency of treatment:
- - each day
- Remarks:
- Doses / Concentrations:
15, 50 and 150 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Positive control:
- none
- Observations and examinations performed and frequency:
- - Clinical Observations: All animals were examined for overt signs of toxicity, ill-health and behavioural change immediately before and alter dosing, and one and five hours after dosing, during the working week. Animals were observed immediately before and after dosing, and one hour after dosing at weekends (except for females during parturition where applicable). During the treatment-free period, animals were observed twice daily, morning and afternoon (once daily at weekends). All observations were recorded.
- Functional Observations: Prior to the start of treatment and at weekly intervals thereafter, all non-recovery animals were observed for signs of functional/behavioural toxicity. Functional performance tests were also performed on tive selected males and females per non-recovery dose level, prior to termination, together with an assessment of sensory reactivity to various stimuli.
- BehaviouralAssessments: Detailed individual clinical observations were performed for each animal using a purpose built arena. The following parameters were observed:
Gait Hyper/Hypothermia, Tremors, Skin colour, Twitches, Respiration, Convulsions, Palpebral closure, Bizarre/Abnonnal/Stereotypic behaviour, Urination, Salivation, Defecation, Pilo-erection, Transfer arousal, Exophthalmia, Tail elevation, Lachrymation
- Functional Performance Tests: Purpose·built 44 infra-red beam automated activity monitors were used to assess motor activity. Animals were randomly allocated to the activity monitors. The tests were performed at approximately the same time each day, under similar laboratory conditions.
- Sensory Reactivity: Each animal was individually assessed for sensory reactivity to auditory, visual and proprioceptive stimuli. The following
parameters were observed: Grasp response, Touch escape, Vocalisation, Pupil reflex, Toe pinch, Startle reflex, Tail pinch, Blink reflex, Finger approach
- Bodyweight: Individual bodyweights were recorded on Day l (prior to dosing) and then weekly for males until termination. Females were weighed weekly until mating was evident. Bodyweights were then recorded on Days 0, 7, 14 and 20 post coitum, and on Days 1 and 4 postpartum. Recovery
animals were weighed on Day 1 (prior to dosing) and then weekly until termination.
- Food Consumption: During the maturation period, weekly food consumption was recorded for each cage of adults.This was continued for males after the mating phase. For females showing evidence of mating, food consumption was recorded for the periods covering Days 0-7, 7-14 and 14-20. For females with live litters, food consumption was recorded on Days 1 and 4 post partum.
- Water Consumption: Water intake was observed daily by visual inspection of water bottles for any overt change.
- Laboratory Investigations: Haematological and blood chemical investigations were performed on five males and five females selected from each non-recovery test and control group on Day 14 (day prior to pairing). Blood samples were obtained from the lateral tail vein. Animals were not fasted prior to sampling.
- Urinalytical investigations were performed on five males selected from non-recovery test and
control group during the final week of treatment and on five males selected from each recovery
group during the final week of the fourteen day treatment-free period.
- Haematology: The following parameters were measured on blood collected into tubes containing potassium EDTA anti-coagulant:
Haemoglobin (Hb), Erythrocyte count (RBC), Haematocrit (Het), Erythrocyte indices, Total leucocyte count (WBC), Differential leucocyte count, Platelet count (PLT), Reticulocyte count
- Blood Chemistry: The following parameters were measured on plasma from blood collected into tubes containing lithium heparin anti-coagulant:
Urea Calcium (Ca++), Glucose Inorganic phosphorus (P), Total protein (Tot.Prot.), Aspartate aminotransferase (ASAT), Albumin Alanine aminotransferase (ALAT), Albumin/Globulin (A/G) ratio (by calculation), Alkaline phosphatase (AP), Sodium (Na+), Creatinine (Creat), Potassium (K+), Total cholesterol (Chol), Chloride (Cl-), Total bilirubin (Bili)
- Urinalysis: The following parameters were recorded on collected urine: Volume, Ketones, Specific Gravity, Bilirubin, pH Urobilinogen, Protein, Reducing Substances, Glucose, Blood - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- - Haematological, blood chemical, organ weight (absolute and relative to terminal bodyweight),
weekly bodyweight gain, litter weights, offspring bodyweights and quantitative functional
performance data were assessed for dose response relationships by linear regression analysis,
followed by one way analysis of variance (ANOVA) incorporating Levene’s test for homogeneity
of variance.
- Where variances were shown to be homogenous, pairwise comparisons were conducted using Dunnett’s test.
- Where Levene’s test showed unequal variances the data were analysed using non-parametric methods: Kruskal-Wallis ANOVA and Mann-Whitney ‘U’ test.
- The non-parametric methods were also used to analyse implantation loss, offspring sex ratio and
landmark developmental markers.
- The haematology variable basophils was not analysed since consistently greater than 30% of the
data were recorded as the same value. - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Females treated with 150 mg/kg/day showed a reduction in group mean bodyweight and bodyweight gain between Day 0 and Day 7 of gestation, although this did not achieve statistical significance [...]. See below.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Mortality.
There were five interim deaths during the study, these were confined to females treated with 150 mg/kg/day. One female (number 76) died during the maturation phase on Day 10. A second female (number 73) was killed in extremis on Day 23 (Day 7 of gestation). Two females were found dead on their Day 22 of gestation (Day 40 of the main study for female 80 and Day 41 of the main study for female 75), The final of the five females (number 72) was killed in extremis on it’s Day 1 of lactation phase (Day 41 of main study).
Clinical signs.
The only toxicological significant observations were detected for the two interim death females that were killed in extremis (numbers 73 and 72), these included incidents of tip-toe gait, hunched posture and pilo erection. One of the females (number 73) also had red/brown staining around the mouth. The deterioration of the females’ condition subsequently led to their termination. No toxicologically significant findings were detected for animals of either sex after the treatment period, or for animals of either sex after the fourteen-day recovery period.
Histopathology.
There were no treatment-related microscopic changes detected for the pituitary or reproductive tissues examined for terminal kill animals after the treatment period. Here were five unscheduled deaths during the course of the study. Three females were found dead and two were killed in extremis, all five females were from the 150 mg/kg/day treatment group. With the possible exception of pyometria reported for female number 72 and focal gastric ulceration for female 73, factors contributing to the death or moribundity in these animals were not evident from histopathological evaluation.
Neurobehaviour.
No treatment-related effects were detected for animals of either sex from all treatment groups after the treatment period. Formal behavioural assessments were not carried out for recovery group animals.
Organ weights.
No treatment-related intergroup differences in organ weights were detected for all treated animals after the treatment period.
Bodyweights.
Females treated with 150 mg/kg/day showed a reduction in group mean bodyweight and bodyweight gain between Day 0 and Day 7 of gestation, although this did not achieve statistical significance it did lead to a statistically significant reduction in bodyweight for these females at Day 1 of lactation.
No effect on bodyweight was detected during maturation for all treated animals; for all treated males and females treated with 50 or 15 mg/kg/day for the remainder of the treatment period and for animals of either sex after the fourteen day treatment free period.
Food Consumption.
Food consumption was reduced for females treated with 150 mg/kg/day during Days 0 to 7 of gestation and Days 1 to 4 of lactation when compared to controls although statistical significance was not achieved.
No treatment related effects in food consumption were detected for any treated males, females treated with 50 or 15 mg/kg/day or animals of either sex after the fourteen day recovery phase.
Water Consumption.
No overt intergroup differences were detected for all animals after the treatment period or for animals after the fourteen day recovery phase.
Haematology.
No treatment-related effects were detected for the haematological parameters investigated prior to mating. Therefore no further haematological analysis was performed.
Blood Chemistry.
No treatment-related intergroup differences in blood chemical parameters were detected prior to mating. Therefore no further blood chemical analysis was performed.
Urinalysis.
No toxicologically significant effects were detected in treated animals when compared to controls, or for animals of either sex after the fourteen day recovery phase.
Reproductive Screening.
Mating.
No adverse effects on mating performance, fertility or gestation lengths were detected.
Offspring Litter Size and Viability.
No intergroup differences were observed for litter size, sex ratio or viability.
Offspring Development.
No treatment-related effects were detected.
Litter Observations.
There were no clinically observable signs of test material toxicity detected in offspring from treated animals. - Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: clinical signs; mortality; body weight during lactation
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- The oral administration of GMT 80% to rats by gavage, at dose levels of 150, 50 and 15 mg/kg bw/day, resulted in no treatment related effects for the males treated with 150 mg/kg bw/day but did result in the death of five females treated with 150 mg/kg bw/day. The
NOEL for systemic toxicity was considered to be 150 mg/kg/day for males and 50 mg/kg bw/day for females.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1977-05-04 to 1979-03-07
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Significant methodological deficiencies
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- only one dose of 2mL/kg; 30 minutes exposure; reporting deficits
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Pel·Freez, Inc., USDA No. 7T-B-16, Rogers, Arkansas 72756
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: 2.38 - 2.84 kg
- Housing: Each animal was housed individually in a suspended, galvanized steel wire cage with dimensions of 14" x 16" x Z4"
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 12 days
- Fasting period before study: 24 h
ENVIRONMENTAL CONDITIONS: No data - Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- In preparation of the test, the sides of the back of each rabbit were clipped using electric clippers. A 3-square-inch patch of hair was left above the dorsal midline. The clipped area of each animal constituted approximately 10 percent of the total body surface area. The animals were then returned to their cages and 24 hours allowed to elapse, before the first mixture application was made. The waiting period permitted the skin to recover from the slight disturbance of the stratum corneum caused by the clipping procedure and also permit the healing of any microscopic abrasions possibly produced during the process. The clipping procedure was repeated at least once a week, but more often if necessary. To prevent oral ingestion of the test material, each animal was fitted with a lightweight, flexible plastic collar which was worn throughout the investigational period.
A mixture of 22.3 parts of - Glyceryl Mono Thioglycolate and 77.7 parts of Part Il Base Lotion #709-B9-1C was evaluated. The test material was applied to the unoccluded partially clipped, 3-square-inch test skin sites at a dose level of 2.0 mL/kg.
REMOVAL OF TEST SUBSTANCE
- Washing: Warm tap water
- Time after start of exposure: 30 minutes - Details on analytical verification of doses or concentrations:
- Dose calculations were made weekly to adjust for changes in body weight.
- Duration of treatment / exposure:
- During the exposure period, the rabbits were placed in restrainers and subjected to a warm air flow from hair dryers installed above the rabbits. After
a 30 minute exposure period, the test sites were thoroughly rinsed with warm aerated tap water and then dried with towels and hair dryer. - Frequency of treatment:
- These dosing procedures were followed 5 days per week for 4 weeks for a total of 20 applications.
- Remarks:
- Doses / Concentrations:
2.0 mL/kg bw
Basis:
nominal per unit body weight - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Positive control:
- not examined
- Observations and examinations performed and frequency:
- Mortality: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: days -12, -7, 14, 21, 28
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Total Leukocyte Count, Erythrocyte Count, Hemoglobin Concentration, Hematocrit Value, Differential Leukocyte Count (Pucent and Absolute), Cell Indices (MCV. MCH and MCHC)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Fasting Blood Glucose Concentration, Blood Urea Nitrogen Concentration (BUN), Serum Alkaline Phosphatase Activity (SAP), Serum Glutamic Pyruvic Transaminase Activity (SGPT), Serum Glutamic Oxalacetic Transaminase Activity (SGOT)
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- At the conclusion of the investigational period, all rabbits were sacrificed. This was followed by a gross pathologic examination.
- Other examinations:
- The weights of the brain, liver, kidneys, spleen, heart, gonads, thyroid glands and adrenal glands were recorded.
- Statistics:
- Kruskal Wallis test and multiple comparison tests
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Mortality: One rabbit died. Rabbit 5-M from the untreated control group died during the 7th test day. The animal exhibited diarrhoea on test days 3, 4 and 5 and died two days later over the weekend. The immediate cause of death was not evident from the pathologic studies but was attributed to naturally occurring disease.
Reactions: No treament related pharmacotoxic symptoms were noted. The test animals exhibited severe hair loss upon repeated dermal exposure to the test material.
Effects on Body Weights: No adverse body weight effects were observed.
Hematology Studies and Clinical Blood Chemistry: No treatment related hematologic effects were noted. - Dose descriptor:
- NOAEL
- Effect level:
- 2 other: mL/kg bw/day
- Based on:
- test mat.
- Remarks:
- 22.3% GMT
- Sex:
- male/female
- Critical effects observed:
- not specified
- Conclusions:
- At 2 mL/kg Glycerol Monothioglycolate 22.3 % showed no treatment related mortality, pharmacotoxic reactions, effects on body weight or hematologic effects. Because no dose finding preleminary studies are available here, these findings can only be used as supporting study.
Reference
Table 1: Summary of Local Skin Reactions
Group |
Local skin reactions after: |
|||
1 application |
3 applications |
5 applications |
7 applications |
|
untreated |
No skin reactions |
No skin reactions |
No skin reactions |
No skin reactions |
treated with test substance |
No skin reactions |
No skin reactions |
Noticeable hair loss 8/10 fissures 1/10 |
Noticeable hair loss 10/10 fissures 3/10 |
Table 2: Continued summary of Local Skin Reactions
Group |
Local skin reactions after: |
|||
10 applications |
12 applications |
15 applications |
20 applications |
|
untreated |
No skin reactions |
No skin reactions |
No skin reactions |
No skin reactions |
treated with test substance |
Noticeable hair
loss 10/10 fissures 1/10 |
Noticeable hair loss 6/10, severe hair loss 3/10, complete hair loss 1/10 |
Noticeable hair loss 4/10, severe hair loss 5/10, complete hair loss 1/10 |
Noticeable hair loss 2/10, severe hair loss 6/10, complete hair loss 2/10 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- Significant methodological deficiencies.
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1977-05-04 to 1979-03-07
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Significant methodological deficiencies
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- only one dose of 2mL/kg; 30 minutes exposure; reporting deficits
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Pel·Freez, Inc., USDA No. 7T-B-16, Rogers, Arkansas 72756
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: 2.38 - 2.84 kg
- Housing: Each animal was housed individually in a suspended, galvanized steel wire cage with dimensions of 14" x 16" x Z4"
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 12 days
- Fasting period before study: 24 h
ENVIRONMENTAL CONDITIONS: No data - Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- In preparation of the test, the sides of the back of each rabbit were clipped using electric clippers. A 3-square-inch patch of hair was left above the dorsal midline. The clipped area of each animal constituted approximately 10 percent of the total body surface area. The animals were then returned to their cages and 24 hours allowed to elapse, before the first mixture application was made. The waiting period permitted the skin to recover from the slight disturbance of the stratum corneum caused by the clipping procedure and also permit the healing of any microscopic abrasions possibly produced during the process. The clipping procedure was repeated at least once a week, but more often if necessary. To prevent oral ingestion of the test material, each animal was fitted with a lightweight, flexible plastic collar which was worn throughout the investigational period.
A mixture of 22.3 parts of - Glyceryl Mono Thioglycolate and 77.7 parts of Part Il Base Lotion #709-B9-1C was evaluated. The test material was applied to the unoccluded partially clipped, 3-square-inch test skin sites at a dose level of 2.0 mL/kg.
REMOVAL OF TEST SUBSTANCE
- Washing: Warm tap water
- Time after start of exposure: 30 minutes - Details on analytical verification of doses or concentrations:
- Dose calculations were made weekly to adjust for changes in body weight.
- Duration of treatment / exposure:
- During the exposure period, the rabbits were placed in restrainers and subjected to a warm air flow from hair dryers installed above the rabbits. After
a 30 minute exposure period, the test sites were thoroughly rinsed with warm aerated tap water and then dried with towels and hair dryer. - Frequency of treatment:
- These dosing procedures were followed 5 days per week for 4 weeks for a total of 20 applications.
- Remarks:
- Doses / Concentrations:
2.0 mL/kg bw
Basis:
nominal per unit body weight - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Positive control:
- not examined
- Observations and examinations performed and frequency:
- Mortality: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: days -12, -7, 14, 21, 28
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Total Leukocyte Count, Erythrocyte Count, Hemoglobin Concentration, Hematocrit Value, Differential Leukocyte Count (Pucent and Absolute), Cell Indices (MCV. MCH and MCHC)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Fasting Blood Glucose Concentration, Blood Urea Nitrogen Concentration (BUN), Serum Alkaline Phosphatase Activity (SAP), Serum Glutamic Pyruvic Transaminase Activity (SGPT), Serum Glutamic Oxalacetic Transaminase Activity (SGOT)
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- At the conclusion of the investigational period, all rabbits were sacrificed. This was followed by a gross pathologic examination.
- Other examinations:
- The weights of the brain, liver, kidneys, spleen, heart, gonads, thyroid glands and adrenal glands were recorded.
- Statistics:
- Kruskal Wallis test and multiple comparison tests
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Mortality: One rabbit died. Rabbit 5-M from the untreated control group died during the 7th test day. The animal exhibited diarrhoea on test days 3, 4 and 5 and died two days later over the weekend. The immediate cause of death was not evident from the pathologic studies but was attributed to naturally occurring disease.
Reactions: No treament related pharmacotoxic symptoms were noted. The test animals exhibited severe hair loss upon repeated dermal exposure to the test material.
Effects on Body Weights: No adverse body weight effects were observed.
Hematology Studies and Clinical Blood Chemistry: No treatment related hematologic effects were noted. - Dose descriptor:
- NOAEL
- Effect level:
- 2 other: mL/kg bw/day
- Based on:
- test mat.
- Remarks:
- 22.3% GMT
- Sex:
- male/female
- Critical effects observed:
- not specified
- Conclusions:
- At 2 mL/kg Glycerol Monothioglycolate 22.3 % showed no treatment related mortality, pharmacotoxic reactions, effects on body weight or hematologic effects. Because no dose finding preleminary studies are available here, these findings can only be used as supporting study.
Reference
Table 1: Summary of Local Skin Reactions
Group |
Local skin reactions after: |
|||
1 application |
3 applications |
5 applications |
7 applications |
|
untreated |
No skin reactions |
No skin reactions |
No skin reactions |
No skin reactions |
treated with test substance |
No skin reactions |
No skin reactions |
Noticeable hair loss 8/10 fissures 1/10 |
Noticeable hair loss 10/10 fissures 3/10 |
Table 2: Continued summary of Local Skin Reactions
Group |
Local skin reactions after: |
|||
10 applications |
12 applications |
15 applications |
20 applications |
|
untreated |
No skin reactions |
No skin reactions |
No skin reactions |
No skin reactions |
treated with test substance |
Noticeable hair
loss 10/10 fissures 1/10 |
Noticeable hair loss 6/10, severe hair loss 3/10, complete hair loss 1/10 |
Noticeable hair loss 4/10, severe hair loss 5/10, complete hair loss 1/10 |
Noticeable hair loss 2/10, severe hair loss 6/10, complete hair loss 2/10 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- Significant methodological deficiencies.
Additional information
The oral administration of GMT 80% to rats by gavage for 28 days OECD 422 at dose levels of 15, 50 and 150 mg/kg bw/day, resulted in no treatment related effects for the males treated with 150 mg/kg bw/day, but did result in the death of five females treated with 150 mg/kg bw/day. The NOEL for systemic toxicity was considered to be 150 mg/kg/day for males and 50 mg/kg bw/day for females. The relative magnitude of the NOEL was confirmed by an oral 90d study with NaTG (OECD 408, Rousseau, 2010). The anion of the NaTG salt is a potential main metabolite of GMT in vivo and very probably responsible for the toxicity of GMT in vivo.
The thioglycolate anion can be formed in vivo after cleavage of the ester bonds of the reaction mass of glycerol and thioglycolic acid. It can be expected that this metabolite of GMT and not glycerol will be responsible for the toxic effects observed in (sub)chronic toxicity studies. Mode of action as well as potential target organs are described in the supporting 90d-study of Rousseau from 2010.Justification for classification or non-classification
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