Troclosene sodium

Endpoint summary

Description of key information

28 day extended to 59 day study drinking water study (rat). Mortalities at mid and high dose levels. High: decreased urine volume and urine creatine in males, decreased absolute liver weight. Effects considered due to aversion to drinking water due to high chlorine concentration.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

115 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Repeat dose oral studies have been performed with both sodium dichloroisocyanurate dihydrate and CYA (or its salt). Upon ingestion of low doses, the chlorinated isocyanurates are rapidly and completely reduced to chloride ion and CYA (or its salt). However, ingestion of large doses could result in residual amounts of available chlorine. Due to the rapid reduction of the chlorinated isocyanurates to CYA in the body, any long-term toxicological effects will be due to CYA not the active substances, therefore long-term studies were performed on CYA or its sodium salt.

Repeat dose (oral)

Sodium dichloroisocyanurate dihydrate:

In a repeat dose subacute study with sodium dichloroisocyanurate for up to 59 days, high chlorine concentrations caused an aversion to the drinking water, hence reduced water consumption and urinary effects at the high dose levels. The NOAEL for males was 115 mg/kg bw/d and for females 178 mg/kg bw/d based on emaciation, deaths.

CYA:

The NOAEL for sub-chronic effects (90-days) is 109 mg/kg bw/day for males based on hyperplasia in the urinary bladder observed in one male in the mid-dose group (Rajasekaran, D (1981) The hyperplasia in males observed in the sub-chronic study has been elucidated in the 2-year combined chronic toxicity and cytogenicity study (Blair, M 1985) where it was seen that male rats were more susceptible to dose related effects during the early stages of the study with reversal of effects over the full dosing period. A small group of male rats were found to be more sensitive to the test material at an early stage of the study, which was considered unusual with chronic toxicity testing. In high dose males the main effects observed were heart and urinary tract lesions. .

CYA has shown no evidence of carcinogenicity via oral exposure in drinking water in doses up to 5375 ppm (equivalent to doses of 1523 mg/kg bw/day for males, and 1582 mg/kg bw/day for females), in carcinogenicity studies in both rat and mouse.

Repeat dose (dermal)

Repeat dose dermal studies have not been performed with the test substance as troclosene sodium is corrosive on contact with skin thereby causing local effects before dermal penetration occurs.

Repeat dose (28 day inhalation) performed with trichloroisocyanuric acid..

A four week inhalation toxicity study was performed with a dust of trichloroisocyanuric acid. Four groups of 10 male and 10 female Sprague-Dawley rats were exposed six hours per day, five days per week for four weeks. The cumulative mean exposure concentrations for Groups I, II, III and IV were 0, 3.2, 10.1 and 31 milligrams per cubic meter (mg/m3), respectively. The average aerodynamic mass median diameter (AMMD) was 3.9 micrometers and the range of geometric standard deviations (GSD) was from 2.4 to 3.8. The LOAEL and NOAEL were estimated to be above 31 mg/m3 for males and females rats.

Justification for classification or non-classification

Repeat dose studies via the oral route using drinking water indicated that systemic toxic effects were due to CYA, with any local effects noted caused by the release of free available chlorine. Therefore, a classification as STOT RE is not justified. Repeat dose studies were not considered relevant via the dermal or inhalation routes.