Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information
There were no treatment related effects on the fertility of the parent generation. Fertility indices, gestation length, litter size, pup survival to weaning and pup weights at parturition and throughout lactation of treated groups, including the sodium control were comparable to those of the controls. An increased incidence of calculi in the urinary bladder in 5375 ppm F2 males was related to the test article. The findings with respect to female water consumption in the high-dose group and the post-mortem urinary bladder findings in the high-dose F2 males had no biologically detrimental effect on the reproductive potential of the parents or on the growth and development of the offspring.

Short description of key information:
The chlorinated isocyanurates are unstable in the body, particularly the stomach, because the free available chlorine is rapidly reduced. CYA, or its salt, is the stable degradation product. Therefore, CYA, or its sodium salt, is the substance of interest for the reproduction studies.
A 3-generation reproductive study (equivalent to EU Method B.35) showed no biologically detrimental effect on the reproductive potential of the parents or on the growth and development of the offspring.
NOAEL (P): ca. 470 mg/kg bw/day (male)
: ca. 950 mg/kg bw/day (female)
NOAEL (F1): ca. 500 mg/kg bw/day (m)
: ca. 910 mg/kg bw/day (f)
NOAEL(F2): ca. 190 mg/kg bw/day (m)
: ca. 970 mg/kg bw/day (f)

Effects on developmental toxicity

Description of key information
Rodwell (1990), performed according to  EPA OPP 83-3 (prenatal developent study) :
NOEL (maternal toxicity): 50 mg/kg bw/day
NOEL (treatogenicity): 500 mg/kg bw/day
There was no evidence of teratogenicity in the absence of maternal toxicity.
Laughlin (1982), performed according to EU Method B.31 (prenatal development study) :
NOAEL (maternal toxicity): 5000 mg /kg bw/day
NOAEL (teratogenicity): 5000 mg/kg bw/day
Test substance was considered non-teratogenic.
Additional information

Maternal Toxicity:

In a study conducted by Rodwell (1990) One female at the 500 mg/kg level and two females at the 50 mg/kg group aborted on gestation days 22, 24 and 26 days respectively.  A slight reduction in bodyweight was observed and appeared to correspond with a slight reduction in litter size. However no treatment-related clinical signs of toxicity or gross abnormalities were observed.

In the study conducted by Laughlin (1982),11 females in the high dose sodium control group (5590 mg/kg/day) died between days 8 and 16 of gestation.  Survival was 100% in all other groups.The mean maternal body weight in the high dose sodium control group was slightly reduced when compared to the control group.

Developmental Toxicity/ Teratogenicity:

Rodwell (1990), showed that there was a statistically significant increase in post-implantation loss at the 500 mg/kg level. This was primarily related to one dam with 7 late resorptions.  No treatment related differences were noted in gravid uterus weight, foetal body weight or foetal malformation data.

In the study conducted by Laughlin (1982), treatment-related effects such as a reduction in group mean foetal body weight and mean foetal crown-rump length and an increase in post-implantation losses were observed in the high-sodium dose group. In the low sodium dose group these parameters were found to be comparable to the controls. In addtion there were some incidences of foetal malformations in the high dose group only.

Justification for classification or non-classification

In the rat teratogenicity study, monosodium cyanurate administered by gavage did not produce a teratogenic response at a dose of 5000 mg/kg bw/day or below. In the rabbit teratogenicity study there was no evidence of developmental toxicity in any of the treated groups.

Oral exposure of monosodium cyanurate in the rat fertility study did not produce any consistent effects on reproductive parameters or offspring toxicity