Reactionmass of dodecan-2-yl prop-2-enoate and dodecan-3-yl prop-2-enoate and dodecan-4-yl prop-2-enoate

Endpoint summary

Description of key information

Two repeated dose studies were conducted on the test article. The results of the studies are:

OECD 413 via inhalation: NOAEC = 201 mg/m^3/day

OECD 421 via ingestion: NOAEL = 700 mg/kg/day

The subchronic repeated dose toxicity potential of MTDID 44430 was evaluated in a 90 -day inhalation study. The study was conducted according to OECD 413 in compliance with OECD GLP. Rats were exposed nose-only to MTDID 44430 6-hours/day, 5-days/week for 13 weeks at target concentrations of 0 (control; n=15/sex), 15 (n=10/sex), 65 (n=10/sex), and 200 mg/m3 aerosol (n=15/sex). Achieved mean actual exposure concentrations in the 15, 65, and 200 mg/m3 groups were 16.1, 65, and 201 mg/m3, respectively. The MMAD (GSD) for the exposure atmospheres were 1.8 µm (1.77), 2.0 µm (1.62), and 2.4 µm (1.80), respectively. Ten animals/sex/group were assigned to the terminal necropsy; the remaining 5 animals/sex in the control and 200mg/m3 dose groups were assigned to a minimum of 4 weeks of recovery. The following parameters and endpoints were evaluated in this study: clinical signs, body weights, body weight gains, food consumption, functional observational battery, motor activity, ophthalmology, clinical pathology parameters (hematology, coagulation, serum chemistry, and urinalysis), bronchoalveolar lavage fluid (BALF) evaluation (chemistry and cytology), gross necropsy findings, organ weights, and histopathologic examinations. The following organ tissues were collected and evaluated for histology and histopathology at the control and 200 mg/m3 test group animals (* denotes that the organs were weighed): adrenal glands*, aorta, bone with marrow, femur (with joint), sternum, bone marrow smear (from femur), brain*, cervix, epididymides*, eyes with optic nerves, gastrointestinal tract, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, harderian glands, heart*, kidneys*, larynx, liver* (sections of 2 lobes), lungs* (including bronchi), lymph nodes, axillary, mandibular, mesenteric, nasal cavity with turbinates, ovaries with oviducts*, pancreas, peripheral nerve, peyer’s patches, pharynx, pituitary gland*, prostate*, salivary glands, seminal vesicles, skeletal muscles, skin with mammary gland (female only; males had skin sections taken from the same anatomic area), spinal cord (cervical, thoracic, lumbar), spleen*, testes*, thymus*, thyroid (with parathyroids)*, tongue, trachea, bladder, uterus*, vagina, and gross lesions (when possible). Additionally, selected tissues (kidney, liver, thyroid, and respiratory tract [lungs, larynx, pharynx, trachea, and nasal cavity with turbinates]) were prepared from all animals in the 15 and 65 mg/m3 test groups for histology. All animals survived to the scheduled necropsies. There were no test substance-related clinical observations of toxicity, nor were there any adverse effects in the FOB or motor activity parameters. No effects on BALF parameters (chemistry and cytology), hematology, coagulation, serum chemistry, urinalysis, or organ weights were noted. There were no test substance-related ophthalmic or macroscopic findings. Test substance-related microscopic changes were limited to the nasal level III females exposed to 65 and 201 mg/m3 at the terminal and recovery time points which was characterized by sporadic, minimal to mild focal olfactory epithelial degeneration. Since the lesions were sporadic in nature and only minimal to mild in severity, these changes were considered non-adverse. Based on the results of this study, a NOAEC of 201mg/m3 (aerosol) was established.

The objective of this study was to provide data on the potential effects of MTDID 44430 on reproductive performance, pup development, and general toxicity of rats by oral exposure. The study was conducted according to OECD 421 under OECD GLP conditions.  Four groups of rats (n= 10/sex) received 0 (control), 40, 150, and 700 mg/kg MTDID 44430 in corn oil as a single daily oral gavage dose. Males were dosed for 14 days prior to mating and continuing through mating, for a minimum of 28 days, until 1 day prior to euthanasia. Females were dosed for 14 days prior to mating and continuing through lactations Day 12. All animals were dosed at approximately the same time each day. The following parameters and endpoints were evaluated in this study: clinical signs, body weights, food consumption, estrous cycles, reproductive performance, parturition, litter viability and survival, anogenital distance, areolae/nipple anlagen, thyroid hormones, gross necropsy findings, organ weights, and histopathology. At necropsy, the adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries (with oviducts), pituitary gland, prostate gland, seminal vesicle (with coagulating gland and fluid), spleen, testes, thymus gland, and thyroid were weighed. Tissue samples of the brain, coagulating gland, kidneys, liver, mammary glands, ovaries with oviducts, pituitary gland, prostate gland, seminal vesicles (2), testes with epididymides (2), vas deferens, thyroid with parathydroids (2), uterus with cervix and vagina, and gross lesions were collected at necropsy from all animals. Histopathological examination was performed on the tissue samples collected (except the liver, kidney, and thyroid) from animals in the control and high-dose groups and gross lesions were examined from all groups. 1 pup/sex/litter was subjected to a complete necropsy examination, with emphasis on developmental morphology and organs of the reproductive system. RESULTS: All F0 animals survived to the scheduled necropsy. No test substance-related clinical findings were noted. There were no statistically significant changes in mean body weight, mean food consumption, reproductive performance, parturition, thyroid hormones, anogenital distance, areolate/nipple anlagen, litter viability and survival. There were no test substance-related changes in organ weight, gross pathology, and histopathology. No internal findings were noted at the necropsy of euthanized pups. Under the conditions of this study, due to the absence of adverse effects at any dosage level, a dosage level of 700 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for F0 systemic toxicity, F0 reproductive toxicity, and F1 neonatal toxicity of MTDID 44430 when administered orally by oral gavage to rats.

Justification for classification or non-classification

Based on the results of the studies, the test article is not classified for repeated dose toxicity according to GHS.