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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1994
Reference Type:
publication
Title:
Newsletter
Author:
JETOC (Japan Chemical Industry Ecology-Toxicology & Information Center)
Year:
1995
Bibliographic source:
JETOC Information Sheet 18, 8-11
Reference Type:
review article or handbook
Title:
Toxicology Profile of 1,1,1-trimethylolpropane
Author:
BIBRA (The British Industrial Biological Research Association)
Year:
1996
Bibliographic source:
Bibra Toxicology International, Information Department, Carshalton , Surrey AM54DS, UK
Reference Type:
publication
Title:
Consensus Report for Trimethylolpropane.Scientific Basis for Swedish Occupational Standards XVI
Author:
Criteria Group for Occupational Standards (ed. Per|Lundberg)
Year:
1995
Bibliographic source:
Arbete Och Haelsa 19, 33-35

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 422
Principles of method if other than guideline:
The study was a combined repeat dose and reproductive/developmental toxicity screening study
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Trimethylolpropane, purity 99.9%. A read across is proposed from this substance based on the structural similarity of the two substances.

Test animals

Species:
rat
Strain:
other: Slc:SD
Details on test animals and environmental conditions:
The animals were male and female Slc:SD rats. At study initiation the males weighed 304-343 g, and the females 196-226 g. The rats were acclimatised for 5 days.
Pregnant females were housed individually. Food and water were provided ad libitum. The room temperature was 22-24°C, humidity 50-60%, with a 12 hour light/dark cycle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The test substance was dissolved in distilled water. Dosing began 2 weeks prior to mating and continued throughout the mating period. Females were dosed throughout pregnancy and up to lactation day (LD) 4. Dosing of the males continued during this period.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Details on analytical verification were not provided.
Details on mating procedure:
Rats were mated 1:1 until pregnancy occurred. Day 0 of pregnancy was defined as the day sperm was present.
Duration of treatment / exposure:
Males were exposed for 45 days, females were exposed for 14 days before mating until LD4.
Frequency of treatment:
Daily
Duration of test:
The animals were 10 weeks old at mating. Males were sacrificed on day 46. Females and their pups were sacrificed on LD 4.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 12.5, 50, 200 and 800 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
12 rats/sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
No further details on study design are available.

Examinations

Ovaries and uterine content:
The ovaries and uterine content were examined after termination, the number of corpora lutea, implantations and early resorptions were recorded.
Fetal examinations:
External foetal examinations were conducted.
Statistics:
Statistical analyses were performed but the methods were not provided.
Indices:
The following reproductive indices were calculated: copulation index, fertility index, gestation index, implantation index, delivery index, birth index and viability index.
Historical control data:
No historical control data were provided.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
There were no maternal signs of toxicity up to the highest dose tested.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
800 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
800 mg/kg bw/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no effects indicative of developmental toxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The NOAEL for maternal and development toxicity was 800 mg/kg/day.

Applicant's summary and conclusion

Conclusions:
No relevant effects were seen in this study: the NOAEL for developmental toxicity was 800 mg/kg bw/d.
Executive summary:

The developmental toxicity of TMP was investigated in a screening study (OECD 422) in rats performed at dose levels of up to 800 mg/kg bw/d. Males were exposed for 45 days, females were exposed for 14 days before mating until LD4. T he ovaries and uterine content were examined after termination, the number of corpora lutea, implantations and early resorptions were recorded. External foetal examinations were conducted. No relevant effects were seen in this study: the NOAEL for developmental toxicity was 800 mg/kg bw/d.