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Administrative data

Description of key information

oral
Rat, Combined repeated dose toxicity/ Reproduction toxicity screenig study: NOAEL systemic toxicity = 100 mg/kg bw due to decreased body weight, food consumption, increased liver weights and microscopic liver changes in the higher dose (GLP, OECD 422, RTC/ Rohm & Haas 2004)
dermal
no data available
inhalation
no data available

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

oral

A GLP conform repeated dose/ reproductive toxicity study was performed with TP-90B RUBBER CHEMICAL according to OECD 422 (RTC/ Rohm & Haas 2004). Groups of 10 Sprague-Dawley rats per sex received TP-90B Rubber Chemical in 0.5% aqueous carboxymethylcellulose at doses of 10, 100 and 800 mg/kg bw/d by gavage. Males were treated for 2 weeks prior to pairing, through pairing until the day before sacrifice. Females were treated for 2 weeks prior to pairing, through the mating and gestation periods up to day 3 of lactation. Dams and offspring were sacrificed on Day 4 post-partum (= at least 43 days). Observations were made as follows:

Fate of females

One mid dose female was sacrificed on Day 0 post-partum for human reasons since signs of dystocia (difficult delivery) were noted.

 

Weekly physical examinations including detailed clinical signs and neurotoxicity assessment (Functional Observation Battery) did not show any treatment-related effects. Daily post-dose observations of clinical signs showed high dose male animals with ataxia,

Semi closed eyes, hunched posture, reduced activity and salivation. Pronation, ataxia, semiclosed eyes, reduced activity, hunched posture, lethargy, twitches, piloerection and salivation were noted at post-dose observations in high dose females.

 

Body weight and body weight gain

Slight decreases in body weight and body weight gain occurred only in high dose females during gestation.

 

Food consumption

Food consumption remained comparable between control and treated groups in both sexes before pairing. Reduced food consumption was noted in high dose females on Days 7 and 14 post-coitum.

 

Motor activity and sensory reaction to stimuli

Motor activity measurements and sensory reaction to stimuli were unaffected by treatment at any dose level in both sexes.

 

Haematology

No toxicologically significant change in haematology values occurred in males or females at any dose level.

 

Clinical chemistry

No toxicologically significant change in any clinical chemistry parameter occurred in malesor females at any dose level.

 

Terminal body weight and organ weights

No differences in terminal body weights were observed between treated and control animals. Absolute and relative liver weights were increased in high dose males and females when compared to controls. All changes were statistically significantly different from controls except the absolute liver weight in females.

 

Macroscopic examination

No macroscopic change was reported at necropsy in the examined organs/tissues of the animals killed at termination that could be considered related to the administration of the test item. The gross changes observed were considered to be incidental or spontaneous in origin.

 

Microscopic examination

No microscopic changes clearly related to test item administration were observed in male or female rats in the low and mid-dose groups. Diffuse hepatocellular hypertrophy (enlarged hepatocytes in all areas of the lobules) occurred in male and female rats of the high dose group. A finding of uncertain significance was observed in the high dose group. Focal germ cell depletion and degeneration in one testis (unilateral) occurred in four high dose male rats. Three of these four rats also had a few exfoliated spermatogenic cells in the lumen of the epididymal tubules.

 

 

In conclusion, following effects were observed only at the high dose (800 mg/kg bw/ day):

- Post-dose clinical signs indicating general effects of toxicity in males and females

- Decreased body weight and body weight gain in females during gestation

- Reduced food consumption in females on days 7 and 14 post-coitum

- Increased liver weights

- Microscopic changes in the liver

The NOAEL of this study was 100 mg/kg bw/d since increases in absolute and relative kidney weights noted in the mid-dose male group only were not interpreted as a clear adverse health effect as this effect was not observed in the high-dose group.

 

 

dermal

no data available

 

 

inhalation

no data available

 


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

Based on the available data on the repeated dose toxicity of hexaoxatricosane no classification is warranted according to the criteria of both, 67/548/EEC and CLP regulation (EC) 1272/2008.