LBX98

Toxicity to reproduction: other studies

Administrative data

Endpoint:

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.

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:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2,4-xylenol and 2,5-xylenol

EC Number:

905-287-4

Cas Number:

1638758-52-7

Molecular formula:

(CH3)2C6H3OH

IUPAC Name:

Reaction mass of 2,4-xylenol and 2,5-xylenol

Test material form:

solid: bulk

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

90 d

Frequency of treatment:

daily

Doses / concentrations

Remarks:

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

RS-Freetext:

 

Male:

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.

 

Female:

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.