Registration Dossier

Administrative data

Description of key information

Based on the available studies, the NOAEL of 113 mg a.i./kg bw/day from the more robust and longer duration 90 day study with the read across substance, C12 -18 TMAC, has been considered further for the hazard assessment of oral route. With regard to the dermal route, due to some deficiencies in the available 28-day dermal study with C16 TMAC (reduced number of test animals per group and limited histopathology), the above NOAEL of the 90-day oral study with C12-18 TMAC has been used as the starting point for hazard assessment of dermal route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
113 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Both studies are conducted according to the OECD guideline as well as in compliance with GLP and have Klimisch score 1. The information requirements for this tonnage band is sufficiently met with the available data.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
10 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
One study available only. The information requirements for this tonnage band is sufficiently met with the available data.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

Study 1. A study was conducted to determine the oral repeated dose toxicity of the read across substance, C12-18 TMAC, according to OECD Guideline 408 and EU Method B.26, in compliance with GLP. Sprague-Dawley rats were administered the test substance at concentrations of 0, 100, 500 or 2000 ppm, corresponding to 0, 22, 113 and 273 mg a.i./kg bw/day) in the diet for 90 d. The highest dose of 2000 ppm was reduced to 1000 ppm from Day 29 onwards due to deterioration in health of the test animals at 2000 ppm. At the highest dose, the treatment-related findings were clinical signs of toxicity, reduced body weight gain and food efficiency, organ weight changes and microscopic changes in the spleen and kidneys. At the mid dose, reduced body weight gain (males) and reduced food consumption, reduced absolute heart weight and higher incidence of haemosiderin accumulation in the kidneys of males was observed. No treatment-related effects were observed at the lowest dose. The NOEL was considered to be 100 ppm (i.e. equivalent to 22 mg a.i./kg bw/day). The changes observed at 500 ppm were considered to be minor, isolated effects associated with the reduced palatability of the test substance and were considered not to represent an adverse health effect. The NOAEL for systemic effects in rats was therefore considered as 500 ppm (i.e. equivalent to 113 mg a.i./kg bw/day) (Jones, 2002).

Study 2. A study was conducted to determine the oral repeated dose toxicity of the read across substance, C16 TMAC, according to a method similar to OECD Guideline 407, in compliance with GLP. Groups of 10 male and female rats were administered 0, 30, 100 and 300 mg/kg bw/day test substance by oral gavage for 28 d. The test substance used was a 24-26% aqueous solution but it is not clear if the doses mentioned were corrected. There were no treatment-related changes at the 30 and 100 mg/kg bw/day. In the high-dose group there was an increase in water consumption, changes in the absolute and relative weights of the adrenals and spleens (inmales) without corresponding effects on haematology, clinical chemistry and histology. The forestomach of the high-dose group showed few microscopic changes, however animals in the high-dose recovery group showed a complete and regular regeneration of the forestomach mucosa. Hence, the forestomach effects were considered to be due to the irritating properties of the test substance rather than symptoms of systemic toxicity. Based on the results of the read across study, the 28 d NOAEL for systemic effects in rats was determined to be 300 mg/kg bw/day (Potokar, 1991).

Dermal

A 28-day repeated dose dermal toxicity study was conducted with the read across substance, C16 TMAC, in New Zealand albino rabbits (both sexes)according to a method similar to OECD Guideline 410. The purity was not specified and the study included a lower than recommended number of animals (i.e., 10/group rather than 20/group as per guideline) and histopathology was performed only on limited organs. The test substance (0 and 10 mg test substance/kg bw/day) was applied to the shaved, intact skin of groups of 5 New Zealand albino rabbits/sex/group for 6.5 to 7 hours, 5 days/week for 4 weeks. Dermal irritation readings were recorded daily. The animals were weighed weekly during the exposure period. Blood was collected for haematology measurements before initiation of dosing and prior to termination. Liver and kidneys weights were recorded at necropsy and limited histopathology was conducted. There were no systemic treatment-related effects on body weights, haematology, organ weights, gross necropsy findings or histopathology. Treated areas of the skin showed mild to marked acanthosis with active mitosis, hyperkeratosis, and partial to extensive necrosis of the epidermis and hair follicles, partly with encrustation and exudate. Based on the results of the read across study, the NOAEL for systemic effects in male and female rabbits was determined to be 10 mg/kg bw/day (Spicer, 1979).


Justification for classification or non-classification

Based on the observed effects and available NOAELs, it can be concluded that C16 -18 and C18 -unsatd. TMAC does not require classification according to CLP criteria (Regulation EC 1272/2008).