Registration Dossier
Registration Dossier
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EC number: 201-063-9 | CAS number: 77-85-0
Toxicological information
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study and GLP
- 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)
- Principles of method if other than guideline:
- Method: OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test.
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- other: Slc:SD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: male: 304-343 g; femalws: 196-226 g
- Housing: pregnant females should be caged individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 50-60
- Photoperiod 12 hrs dark / 12 hrs light - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- dosing of both sexes should begin 2 weeks prior to matingm continued through mating period
males: dosing continued up to the day when females are killed
females: dosing continued throughout pregnancy and up to day 4 of lactation - Details on mating procedure:
- One female to one male until pregnancy occurs.
Day 0 of pregnancy is defined as the day sperm is found. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- details not given
- Duration of treatment / exposure:
- Exposure period: male, 45 days; female, from 14 days before mating to day 3 of lactation
.
Duration of test: terminal kill: male, day 46; female and pups, day 4 of lactation. - Frequency of treatment:
- Daily
- Details on study schedule:
- Age at mating of the mated animals 10 weeks
- Remarks:
- Doses / Concentrations:
0, 12.5, 50, 200, 800 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- as requested by OECD TG 422
- Positive control:
- no
- Parental animals: Observations and examinations:
- at least once per day:
--behavioural changes, signs of difficult or prolonged parturition, mortality and all signs of toxicity
cage side observations:
changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system fucnction
--food consumption, males and females should be weighed
--duration of gestation, examination of the litter as soon as possible, number and sex of pups, stillbirth, live birth, pup weight, and the presence of gross anomalies
--clinical examinations: hematologym clinical chemistry, urinalysis
--pathology: gross necropsy, histopathology - Oestrous cyclicity (parental animals):
- no data,
- Sperm parameters (parental animals):
- no data
- Litter observations:
- 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, physical or behavioural abnormalities,
GROSS EXAMINATION OF DEAD PUPS:
yes, for external abnormalities; - Postmortem examinations (parental animals):
- pathology: gross necropsy, histopathology
- Postmortem examinations (offspring):
- external malformation
- Statistics:
- yes but method not mentioned
- Reproductive indices:
- number of mated pairs
number of copulated pairs
copulation index
number of pregnant animals
fertility index
pairing days until copulation
implantation index
delivery index - Offspring viability indices:
- number of pups born,
number of pups alive
birth index
live birth index
sex ratio
number of pups alive on day 4
viability index
body weight of F1 pups on day 4 - 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:
- effects observed, treatment-related
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 800 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: based on no signs indicative for reproductive / developmental toxicity up to the highest test dose.
- Dose descriptor:
- other: NOAEL (general toxicity)
- Effect level:
- 200 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: see section 7.5.1
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 800 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: based on no signs indicative of developmental toxicity up to the highest test dose
- Reproductive effects observed:
- not specified
- Executive summary:
Trimethylolpropane was studied for oral toxicity in an OECD TG 422 (combined repeat dose and reproductive/ developmental toxicity screening test) at doses of 0. 12.5, 50, 200, and 800 mg/kg bw/day given by gavage. No signs indicative of reproductive/ developmental toxicity were observed . The NOAEL for reproductive performance and offspring development were both 800 mg/kg bw/day. The NOAEL (general toxicity) was 200 mg/kg bw/day (MHLW 1994).
Reference
BODY WEIGHT (PARENTAL ANIMALS)
800 mg/kg bw/day: males and females: lowered during premating period when compared to controls
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects of the test substance on copulation, fertility or estrus cycle of rats, on delivery and on dams during the lactation period.
ORGAN WEIGHTS (PARENTAL ANIMALS)
males:
800 mg/kg bw/day, significant: absolute mean liver weight: 13.92 g versus 11.55 g of controls
800 mg/kg bw/day, significant. relative mean liver weight: 3.647 g% versus 2.926 g% of controls
females
800 mg/kg bw/day, non-significant: absolute mean liver weight: 11.54 g versus 10.54 g of controls
800 mg/kg bw/day, non-significant. relative mean liver weight: 4.237g% versus 4.014g% of controls
GROSS PATHOLOGY (PARENTAL ANIMALS)
HISTOPATHOLOGY (PARENTAL ANIMALS)liver:
Necropsy revealed hypertrophy of th liver in 3 male rats receiving 800 mg/kg.
Histopathological examintion revealed no definite morphological lesions.
kidneys:
Slight basophilic alteration of the renal tubular epithelial cells was observed in
1 female receiving 50 mg/kg, in 2 females receiving 200 mg/kg and in 5 females receiving 800 mg/kg.
These changes were not unequivocally attributable to the test substance administration, because of their limited distribution and limited degree,
and because similar lesions were observed in male rats of all groups including the controls.
800 mg/kg bw/day: males and females: lowered during premating period when compared to controls
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects of the test substance on copulation, fertility or estrus cycle of rats, on delivery and on dams during the lactation period.
ORGAN WEIGHTS (PARENTAL ANIMALS)
males:
800 mg/kg bw/day, significant: absolute mean liver weight: 13.92 g versus 11.55 g of controls
800 mg/kg bw/day, significant. relative mean liver weight: 3.647 g% versus 2.926 g% of controls
females
800 mg/kg bw/day, non-significant: absolute mean liver weight: 11.54 g versus 10.54 g of controls
800 mg/kg bw/day, non-significant. relative mean liver weight: 4.237g% versus 4.014g% of controls
GROSS PATHOLOGY (PARENTAL ANIMALS)
HISTOPATHOLOGY (PARENTAL ANIMALS)liver:
Necropsy revealed hypertrophy of th liver in 3 male rats receiving 800 mg/kg.
Histopathological examintion revealed no definite morphological lesions.
kidneys:
Slight basophilic alteration of the renal tubular epithelial cells was observed in
1 female receiving 50 mg/kg, in 2 females receiving 200 mg/kg and in 5 females receiving 800 mg/kg.
These changes were not unequivocally attributable to the test substance administration, because of their limited distribution and limited degree,
and because similar lesions were observed in male rats of all groups including the controls.
External examination of pups revealed no increase in the incidence of abnormalities. Body weight gain of pups was normal up to day 4 of the lactation period. Stillborn, dead pups and pups killed at day 4 of lactation period showed no abnormal gross lesions be attributable to treatment with the test substance.
No effects of the test substance on copulation, fertility or
estrus cycle of rats, on delivery and on dams during the lactation period.
External examination of pups revealed no increase in the incidence of abnormalities. Body weight gain of pups was normal up to day 4 of the lactation period.
Stillborn, dead pups and pups killed at day 4 of lactation period showed no abnormal gross lesions be attributable to treatment with the test substance.
External examination of pups revealed no increase in the incidence of abnormalities. Body weight gain of pups was normal up to day 4 of the lactation period.
Stillborn, dead pups and pups killed at day 4 of lactation period showed no abnormal gross lesions be attributable to treatment with the test substance.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 800 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Guideline study rated Klimisch 1 (reliable without restriction).
Justification for classification or non-classification
Additional information
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