Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
04 August 2011 - 17 April 2012
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The study has many deviations and the information in the report is incomplete.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Principles of method if other than guideline:
The study has many deviations and the information in the report is incomplete.
- evaluation of oestrus cycle and sperm parameters.
- organ weights
- chemical analysis of concentrations in feed (plus validation)
- Only summary tables provided. Tables with individual data should be included.
- (individual) tables on clinical observations
- No macroscopic post-mortem evaluations reported and no full histopathology report on observations per animal. Only acute testicular necrosis and 4 pelvic dilatations in P male of 2500ppm group is mentioned.
- No information reported on pup observations (anomalies), neuro-behavioural evaluations, and specifically sexual maturation (vaginal opening or balano-preputial separation)
- No specific litter and pup information reported (pups/dam, sex ratio). Table on pup survival table 16 and 18 are unclear as to how many pups died when.
- Information on implantation sites in uterus missing. Therefore information on post-implantation loss is missing.
- The laboratory has no GLP accreditation
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Name: α,α,α',α'-tetramethyl-m-xylene-α,α'-diol
Lot No.: 101155
odourless white solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Remarks:
Test substance was milled by a mortar and sieved by 100 mesh for the test.
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: until proof of mating or up to 2 weeks
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After ?? days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no data
- After successful mating each pregnant female was caged (how): no data
- Any other deviations from standard protocol: see above
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
males: mating period
females: mating period, up to and including lactation
Frequency of treatment:
daily via the diet
Details on study schedule:
F1: Four male and four female pups were randomly selected as representatives of each litter. After weaning, the breeding programme was repeated with the F1 parents to reduce the F2A litters after a 10 week pre-mating period.
F2: The pups were humanely killed and examined in 3 weeks age.
Doses / concentrations
Remarks:
Doses / Concentrations:
0,150, 600, 2500, 10000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
P0: 30
F1: 4 from each litter
Control animals:
yes

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Abstract from study report:

Results

There were reductions in bodyweight during pre-mating period in F0 and F1 animals receiving 10000 ppm combined by reduced bodyweight in F1 and F2 pups. There were no effects of α,α,α',α'-tetramethyl -m-xylene-α,α'-diol on reproductive parameters and dose levels up to and including 10000 ppm.

Conclusions

There were no effects of α,α,α',α'-tetramethyl-m-xylene-α,α'-diol on reproductive parameters at dose levels up to 10000 ppm.

There were signs of toxicity in parents and offspring receiving 10000 ppmα,α,α',α'-tetramethyl-m-xylene-α,α'-diol, seen as reduced bodyweight.

The NOAEL was 2500 mg/kg diet, equivalent to 168.0 mg/kg bw/d for males, 253.9 mg/kg bw/d for females.

Applicant's summary and conclusion

Conclusions:
There were no effects of α,α,α',α'-tetramethyl-m-xylene-α,α'-diol on reproductive parameters at dose levels up to 10000 ppm.
There were signs of toxicity in parents and offspring receiving 10000 ppmα,α,α',α'-tetramethyl-m-xylene-α,α'-diol, seen as reduced bodyweight.
The NOAEL was 2500 mg/kg diet, equivalent to 168.0 mg/kg bw/d for males, 253.9 mg/kg bw/d for females.
Executive summary:

Abstract from study report:

Study design

Groups of 30 male and female (F0 parents) Wistar rats were fed diet containing 0(control), 150, 600, 2500 or 10000 ppmα,α,α',α'-tetramethyl -m-xylene-α,α'-diol.After 10 weeks, the animals were mated and allowed to rear the F1A litters to weaning. The breeding programme was repeated with the F1 parents selected from the F1A offspring to produce the F2A litters after a 10 week pre-mating period. Test diets were fed continuously throughout the study.

Results

There were reductions in bodyweight during pre-mating period in F0 and F1 animals receiving 10000 ppm combined by reduced bodyweight in F1 and F2 pups. There were no effects of α,α,α',α'-tetramethyl -m-xylene-α,α'-diol on reproductive parameters and dose levels up to and including 10000 ppm.

Conclusions

There were no effects of α,α,α',α'-tetramethyl-m-xylene-α,α'-diol on reproductive parameters at dose levels up to 10000 ppm.

There were signs of toxicity in parents and offspring receiving 10000 ppmα,α,α',α'-tetramethyl-m-xylene-α,α'-diol, seen as reduced bodyweight.

The NOAEL was 2500 mg/kg diet, equivalent to 168.0 mg/kg bw/d for males, 253.9 mg/kg bw/d for females.