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EC number: 601-601-6 | CAS number: 119345-04-9
Screening studies from two bracketing category members are available (refer to full ADPODS Category Justification document).
Based on the study results, no adverse effects on reproduction and fertility were observed and are expected for DOWFAX 2A1. Furthermore, extended one generation reproductive toxicity study is being proposed by the Registrant.
This study was conducted for The Dow Chemical Company to generate limited information concerning the effects of the test article, DOWFAX C6L, on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus, and parturition. Three treatment groups of 12 male and 12 female Sprague-Dawley [Crl: CD® (SD)] rats were administered the test article at dose levels of 54, 181, and 904 mg/kg/day of DOWFAX C6L (corresponding to 125, 417, and 2083 mg/kg/day bulk material dose levels, based on 43.4% purity) at a dose volume of 4 mL/kg. One additional group served as the control and received the vehicle, distilled water, at the same volume and dosing regimen as the treated groups. The vehicle control and test article were administered for at least 42 consecutive days to males (14 days premating, 14 days of mating, and 14 days after completion of the mating period after all females had delivered) and up to 54 days in females dependent on reproductive performance (14 days of premating, 14 days of mating [maximum], 22 days gestation and 4 days postpartum).
Observations included clinical signs, body weights, and food consumption during the premating, gestation, lactation, and postmating periods. After 2 weeks of vehicle or test article administration, the females were cohabited with males, one male to one female, from the same treatment group, for up to 14 days. Vaginal smears (lavage) were evaluated daily in females during the 14-day period to establish estrous cyclicity. Once mating was confirmed on Gestation Day 0 (GD 0), females were separated from the male for the remainder of gestation, and allowed to deliver and nurse litters until Lactation Day (LD) 4. Observations of the F1 (first generation offspring) pups included survival at birth and during lactation, individual pup body weights and sex, and clinical examinations on LD 0 and 4. Pups were euthanized and externally examined on LD 4. Complete necropsies were performed on all adult animals and protocol-designated organs and tissues were weighed and microscopically examined.
Two males and four females in the high dose group (904 mg/kg/day) died during the course of the study. The deaths did not appear to have been related to a mechanical dosing error, as no evidence of esophageal perforation was noted at necropsy. For the males, the deaths occurred on study days 49 and 57. For the females, the deaths occurred on premating day 4, GD 16, LD 1 and LD 3. The death of these animals was considered to be test article related.
Two OECD 422 studies were conducted with category members (DOWFAX C6L and 8390; refer to full read-across ADPODS category justification document). There were no observed effects on fetal or neonatal survival, litter sizes or individual pup appearance at parentally toxic dose levels. The data from the category substances is considered sufficient to assess reproductive toxicity potential of DOWFAX 2A1. Based on the lack of reproductive toxicity observed in the studies with category members, it is argued that the REACH substance is also not a reproductive toxicant. Further testing (OECD 443) is proposed and will be conducted for DOWFAX 2A1.
Short description of key information: Reproductive/developmental screening studies conducted on category member substances (DOWFAX C6L and 8390) Justification for selection of Effect on fertility via oral route: GLP guideline study for the shortest ADPODS category member.
Chernoff developmental toxicity study on DOWFAX C6L category member (refer to full ADPODS Category Justification document).
Rabbit developmental toxicity study (OECD 414) is proposed for DOWFAX 2A1.
A Chernoff test was conducted using DOWFAX* C-6 A1kylated Sodium Sulfonate (DCA) (an alkylated diphenyl oxide compound) in which pregnant female Fischer 344 rats were administered dose levels of 0, 300 or 1000 mg/kg/day of DCA in deionized water by gavage on days 6 through 15 of gestation. These animals were then allowed to deliver their litters and the litters were evaluated for size, neonatal growth and survival.
Administration of oral doses of 300 or 1000 mg/kg/day of DCA during gestation produced significant depression in maternal weight gain at both dose levels. Evaluation of the litters for mean litter size, neonatal growth and survival through the first 3 days post-partum did not reveal any significant adverse effects at either dose level. Thus, DCA did not appear to have a selective developmental toxicity even at dose 1evels producing significant maternal toxicity.
In two OECD 422 studies with category members, there were no observed effects on fetal or neonatal survival, litter sizes or individual pup appearance at parentally toxic dose levels. In addition to these screening studies, an additional screening study for developmental toxicity was performed on the DOWFAX C6L ADPODS category member. Oral administration of this substance on days 6 through 15 of gestation at dose levels of 300 and 1000 mg/kg/day produced significant depressions in maternal weight gain during the treatment period, with no significant adverse effects on reproductive parameters in either group. Thus, it does not appear that ADPODS are developmental toxicant even at dose levels producing significant maternal toxicity. The data from the ADPODS substances is considered sufficient to assess the developmental toxicity of the REACH substance (refer to full read-across ADPODS category justification document).
Based on the lack of developmental toxicity observed in the studies with ADPODS category members, it is argued that DOWFAX 2A1 is also not a developmental toxicant. Further developmental toxicity study in rabbit (OECD 414) will be conducted for DOWFAX 2A1. Justification for selection of Effect on developmental toxicity: via oral route: GLP compliant study for the shortest ADPODS category member.
No CLP classification is required for the reproductive toxicity endpoint for DOWFAX 2A1.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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