API TR 400:1993 pdf download.A Preliminary Study of the Effect of Toluene on Pregnancy of the Rat (Inhalation Exposure)
Sexually mature (10 – 13 weeks old,. weight range 194 – 268 g) Specific Pathogen Free female rats (Crl: CD R (SD) BR VAF/Plus strain) which were time -mated to identified males of the same strain, in the Reproductive Toxicology facility were forwarded to the Inhalation Toxicity facility. The day of mating, &S judged by the appearance of sperm in the vaginal smear or by the presence of & vaginal p1ug, was considered as Day 0 of pregnancy. Time- mated animals were assigned to six groups on Day 0 of pregnancy taking into account, where possible, the distribution of males to which the females were mated and the bodyweight of the animals. Following allocation, the animals were ear tattooed to give individual identification. Prior to the comnencement of treatment, all animals were inspected by a Veterinary Officer . Animal room controls for temperature and relative humidity were set at 21士3°C and 55士15% respectively. During the course of the study recorded values for temperature ranged from 21土3°C and for relative humidity 61土17%. Lighting was controlled to give 12 hours light (8 am to 8 pm) and 12 hours dark per 24 hours. The animals were individually housed in suspended stainless steel cages equipped with solid and mesh sides and mesh floor. The cages constituting each treatment group were held on separate batteries, each in & separate ventilated cabinet in order to minimise the poss ibility of inhalation of test substance vapour from the fur of, or exhaled by, rats in other test groups Throughout the study, each cage was identified by a label coloured according to the group and recording the study schedule number, animal numbers , details of treatment and the nane of the Study Supervisor. The dates treatment commenced and terminated were identified on each cage label A1l animals were given free access to Biosure Laboratory Animal Diet No. 1 and to tap water other than during inhalation exposure when food and water were withheld. (Quality Assurance Aspects for Food and Water are presented in Addenda 4 and 5).
(a) Clinical signs and mortalities (Table 1, Appendices 1 and 2, Addendum l) Clinical signs associated with treatment were apparent at 3500 and 5000 ppm and were mainly confined to or immediately after the 6 hour daily exposure period. These signs consisted mainly of those indicative of a gradual narcosis with a degree of anaesthesia and increased in severity and duration with dosges. Related signs persisted through to initial examination the following day in 3animals(1at3500ppmand2at5000ppmfor2and1days respectively). There were no signs considered related to trea tment at 500，1000 and 2000 ppm.