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46214301.DER.pdf
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46214301
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Terbufos
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13071-79-9
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105001
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Kaufmann, W.; Schneider, S.; Deckardt, K.; et. al. (2004) BAS 316 I (terbufos) - Developmental Neurotoxicity Study in Wistar Rats Oral Administration to the Dames and Pups (Gavage): Final Report. Project Number: 66R0090/02012, 2004/1007841.Unpublished study prepared by BASF Aktiengesellschaft. 863 p.
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2004.0
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In a developmental neurotoxicity study (MRID 46214301), Terbufos (88.88% a.i., batch # AC 12251-100) was administered in corn oil to 42 pre-mated female Wistar (CrlGlxBrlHan:WI) rats/dose by gavage at doses of 0, 0.01, 0.08 and 0.15 mg/kg/day from gestation day (GD) 6 through postnatal day (PND) 10 in a volume of 5 mL/kg body weight. The test material was administered to offspring at the same doses from post-natal days 11 through 21. A Functional Observational Battery (FOB) was performed on 10 dams/dose on gestation days 7 and 14, and on 10 dams/dose on lactation days 7 and 14. On postnatal day 4, litters were culled to yield four males and four females (as closely as possible). Offspring were allocated for detailed clinical observations (FOB) on PND 4, 11, 21, 35, 45, and 60; assessment of motor activity on PND 13, 17, 21, and 60; auditory startle response habituation on PND 24 and 60; learning and memory on PND 23 and 60. On postnatal day 22 and 60, the whole brain was collected from 10 pups/sex/dose level for micropathologic examination and morphometric analysis. Brain, erythrocyte, and serum cholinesterase activities were measured in offspring (10/dose group) on days 4 and 21 and in dams (10/dose group) on postnatal day 21. Pup physical development was assessed by body weight. The age of sexual maturation (vaginal opening in females and preputial separation in males) was assessed.
In dams, there were no treatment-related effects on mortality, clinical signs, body weight, or food consumption. No treatment-related effects on reproductive parameters were observed. High-dose dams exhibited toxicologically significant inhibition in erythrocyte (26% inhibition; p<=0.01) and brain (33% inhibition; p<=0.01) cholinesterase activity on PND 21. Erythrocyte cholinesterase activity was inhibited 13% (p<=0.05) in mid-dose dams; however, this effect, while treatment-related, is not considered toxicologically significant due to the small magnitude of change. No other cholinesterase activity effects were noted in dams on PND 21.
The maternal LOAEL was 0.15 mg/kg/day based on inhibition of erythrocyte and brain cholinesterase activity. The maternal NOAEL was 0.08 mg/kg/day.
In offspring, there were no treatment-related deaths, clinical signs or effects on birth weight, developmental landmarks, FOB parameters, auditory startle reflex, learning and memory, brain weight, brain morphology, or neuropathology. At the high dose (0.15 mg/kg/day), male and female offspring body weight was approximately 4-6% lower from LD 11 through weaning at day 21. Body weight gain was decreased for high-dose males and females during lactation days 1-11 (up to 11% decrease) and lactation days 12-13 (up to 14% decrease). No body weight effects were noted for low- or mid-dose pups during lactation. There were no toxicologically-significant post-weaning body weight effects. There were treatment-related increases in motor activity at the mid and high dose groups. On PND 13, there were increases in males at the mid (35%) and high (58%) dose groups and in females at the mid (34%) and high (19%) dose groups. On PND 17 there were increases in males at the mid (18%) and high (26%) dose groups and in females at the mid (15%) and high (64%) dose groups.
No treatment-related changes were noted in serum, erythrocyte or brain cholinesterase activity for male or female pups on PND 4. On PND 21, significant dose-related inhibition (p<=0.05 or 0.01) of serum (56-86% decrease), erythrocyte (47-84% decrease), and brain (38-75% decrease) ChE activity were observed in mid- and high-dose males and females. No treatment-related effects were noted for low-dose animals.
The offspring LOAEL was 0.08 based on increased motor activity in males and females on PND 13 and 17 and inhibition of serum, erythrocyte, brain cholinesterase activity in both sexes. The NOAEL was 0.01 mg/kg/day.
This study is classified Acceptable/Non Guideline and may be used for regulatory purposes, however it does not satisfy the guideline requirement for a developmental neurotoxicity study in rats (OPPTS 870.6300, §83-6); OECD 426 (draft) at this time pending a comprehensive review of all available positive control data.
[Note - This classification scheme is applicable only to Developmental Neurotoxicity (DNT) studies. The DNT Work Group determined that this study can be classified as Acceptable. This study does not satisfy the guideline requirements for a developmental neurotoxicity study and is classified as NonGuideline pending review of all available positive control data. J. Rowland, 09/28/2005].
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Developmental-Neurotoxicity
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NA [83-6, Developmental Neurotoxicity|870.6300, Developmental neurotoxicity study]
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Oral
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No Duration Period; gavage; maternal GD 6 to PND 10;
offspring PND 11 to PND 21
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52438.0
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2005-09-28
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2005-10-28
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Added by
Madison Feshuk
on Apr 25, 2022
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