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Diss Factsheets

Toxicological information

Toxicity to reproduction: other studies

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Administrative data

toxicity to reproduction: other studies
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
The reproductive toxicity of the individual (o-, m- and p-) cresol isomers has been investigated in three separate two-generation toxicity studies. No effects on fertility were seen in any study at the high dose level of 450 mg/kg bw/d. General toxicity (increased mortality and in clinical signs including hypoactivity, ataxia, twitches, tremors, prostration, gasping, rapid respiration and perioral wetness) were observed at dose levels of 175 and 450 mg/kg bw/d, resulting parental NOAELs of 30 mg/kg bw/d. Reduced pup weight and viability were seen at the highest (and parentally toxic) dose level of 450 mg/kg bw/d, leading to NOAEL values of 175 mg/kg bw/d. OECD 422 screening studies available for xylenol (mixed isomers) and ethylphenol (mixed isomers) both report and absence of effects on fertility and reproductive NOAEL values of 245 mg/kg bw/d. The Category substances therefore consistently demonstrate a lack of reproductive toxicity. Read-across is therefore proposed to the study with xylenol as the closest structural analogue among the Category members.
Developmental toxicity studies in the rat are available for the individual (o-, m- and p-) cresol isomers. Each study identified significant maternal toxicity (mortality, clinical signs, bodyweight deficits) at the high dose level of 450 mg/kg bw/d, resulting in maternal NOAELs of 175 mg/kg bw/d for each isomer. Slight fetotoxicity was observed at 450 mg/kg bw/d for o-cresol (one visceral variation: dilated lateral ventricles of the brain) and for p-cresol (reduced foetal weight, reduced skeletal ossification). There were no foetal effects with m-cresol at any dose level.

Data source

Materials and methods

Principles of method if other than guideline:
Type: other: subchronicMethod: other: determination of sperm motility and concentration in males and length of oestrus cycle and vaginal cytology following repeated dose according EPA OPP 82-1
GLP compliance:
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 2,4-xylenol and 2,5-xylenol
EC Number:
Cas Number:
Molecular formula:
Reaction mass of 2,4-xylenol and 2,5-xylenol
Test material form:
solid: bulk

Test animals


Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
90 d
Frequency of treatment:
Doses / concentrations
Doses / Concentrations:0, 1250, 5000 ppmBasis:
Control animals:
yes, concurrent no treatment
Details on study design:
Duration of test: 90

Results and discussion

Any other information on results incl. tables




Reproductive organ weights (R. testicle and R. epididymidis) showed no difference to the respective controls; epididymal tail weight was significantly reduced when compared to the respective control.

Spermatogonial measurements revealed no findings.



Mean estrous cycle length was significantly prolonged at 20000 ppm.

Applicant's summary and conclusion

Executive summary:

The above results are suitable to be used for read across for Reaction mass of 2,4-xylenol and 2,5-xylenol, due to the category being based on structural similarity and comparable physicochemical properties, leading to similar (eco)toxicological properties.