Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data is contained in EU risk assessment report of the substance - credibility is assumed. Reference to origin (Hunter et al.)

Data source

Referenceopen allclose all

Reference Type:
other: EU risk assessment report
Title:
No information
Author:
Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany
Year:
2009
Bibliographic source:
European Union Risk Assessment Report, 4-tert-butylbenzoic acid, CAS No: 98-73-7, EINECS No: 202-696-3, p. 58, Final Approved Version, July 2009
Reference Type:
publication
Title:
No information
Author:
Hunter et al.
Year:
1965
Bibliographic source:
Hunter CG, Chambers PL and Stevenson DE (1965). Studies on the oral toxicity of p-tertbutyl benzoic acid in rats. Fd Cosmet. Toxicol. 3, 289-298.

Materials and methods

Principles of method if other than guideline:
90 d repeated dose oral toxicity study with rats (male/female), uptake of the test substance with the diet, examination of substance-induced effects.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: test substance in diet

Test animals

Species:
rat
Strain:
other: Carworth farm
Sex:
male/female

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Unscheduled deaths of 9 of ten high dose males occurred by day 34, all females receiving 10000 ppm died by day 53. From the group receiving 3160 ppm, two males died by day 42 and six further males were killed moribund. Two mortalities and one female rat to be killed were also seen in the female group at 3160 ppm. Hematuria has been observed in one male and two females receiving 3160 ppm. Hind limb paralysis was reported for one male and one female exposed to diet concentration of 3160 ppm and one female at 1000 ppm. Kyphosis was observed in three rats receiving 3160 ppm and suspected to occur secondarily to chronic renal failure.

Final body weights were significantly depressed in males at diet concentrations of 316 and above and in female rats at 1000 ppm and above. The feed consumption was reduced in the two top doses to 50-70% of the control values and was not affected in the other dose groups. No treatment-related effect was seen on hematology parameters other than reduced erythrocyte counts in the surviving male treated with 10000 ppm and a shift towards increased percentages of neutrophils and reduction in lymphocyte counts at diet concentrations of 3160 ppm (surviving males and females) and of 10000 ppm (1 male survivor). Clinical chemistry findings showed reduced levels of total protein for male groups receiving 100 to 1000 ppm; urea concentrations were increased in males and female rats at diet concentrations ≥1000 ppm in a dose-related fashion.

Urinalysis revealed increased urine volume and reduced urine osmolality in rats treated with diet concentrations at 3160 ppm and above; protein concentrations were elevated in animals the 10000 ppm dose groups.

Relative organ weights of the liver and the kidneys increased at all diet concentrations. The testes to body ratio decreased in all male dose groups.

Gross findings in dying and sacrificed rats of the two top doses showed congested and speckled livers and hydronephrosis, hydroureter, ureteral obstructions, hematuria in the urinary tract. Bilateral atrophy of the testes was found in males of all dose groups. Microscopically, sinusoidal congestion and fatty degeneration of centrilobular hepatocytes were found (the ‘fatty’ nature was not confirmed by specific staining procedures). Hydronephrosis was confirmed by histopathological examination for males at ≥3160 ppm and female rats at 10000 ppm. Intra-luminal cell debris, necrosis of the tubular epithelium, and papillary necrosis were reported as the causes of the obstructive urinary tract lesions.

Renal tubular necrosis and papillary necrosis was evident in treated male and female rats of all dose groups. The testes atrophy was related to degenerated epithelium of seminiferous tubules.

A NOAEL could not be determined in this early study; 100 ppm (6 mg/kg bw/d for male rat, 8 mg/kg bw/d for female rats) is the LOAEL for oral subchronic administration of 4-tertbutylbenzoic acid.

Applicant's summary and conclusion

Conclusions:
According to the results in this study the oral LOAEL of the test substance is 100 ppm (6 mg/kg in male rats, 8 mg/kg in female rats).