reaction mass of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-2H -isothiazol-3-one

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

457 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1.23 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

660 mg/kg bw

Additional information

The acute toxicity studies were conducted on active substance as manufactured ACTICIDE®14 (Thor) and KathonTM886F (Dow) or on C(M)IT/MIT formulations (Kathon TM886 all magnesium formulations which is considered as equivalent to the technical grade Kathon™ 886F). The results, expressed as a C(M)IT/MIT active ingredient basis are presented in the table 3.2-1.

The acute oral LD50 of C(M)IT/MIT in rats ranges from 457 to 472 mg/kg bw (corr. to 64 to 66 mg a.i./kg bw). Dead animals show effects on stomach and intestines which are consistent with the corrosive properties of C(M)IT/MIT. Therefore, C(M)IT/MIT meets the EU criteria for

classification as ‘Harmful if swallowed’ and should be classified as Xn; R22 (corr. to ‘Toxic if swallowed’, R25 for C(M)IT/MIT 3:1) according to the directive 67/548/EC. A classification as Acute Tox 4 / H302: Harmful if swallowed is required according to the regulation 1272/2008/EC (corr. to Acute Tox. 3 /H 301: Toxic if swallowed for C(M)IT/MIT 3:1).

The acute dermal LD50 of KathonTM886 (A6.1.2/01) in male rabbits was 660 mg/kg (corr. to 87 mg a.i/kg bw). In rats (A6.1.2/01), the acute dermal LD50 of ACTICIDE 14 was > 1008 mg/kg (corr. to 141 mg a.i/kg b.w). Observed effects are restricted to local effects or are subsequent to local effects. C(M)IT/MIT should be classified ‘Xn; R21 ‘Harmful in contact with skin’ according to the EU criteria for classification (corr. to ‘Toxic in contact with skin’, R24 for C(M)IT/MIT 3:1) according to the directive 67/548/EC. A classification as Acute Tox 3 / H312: Harmful in contact with skin is required according to the regulation 1272/2008/EC (corr. to Acute tox 2 / H 310: Fatal in contact with skin for C(M)IT/MIT 3:1) .

After acute exposure by inhalation, C(M)IT/MIT induces effects in relation with its corrosive properties. The 4-hr nose-only acute inhalation LC50 of C(M)IT/MIT in rats ranges from 1.23 to 2.36 mg/L air (corr. to 0.171 to 0.33 mg a.i./L air). The effects observed are consistent with the clinical signs of respiratory irritation. It is likely that the deaths resulted from excess fluids in the respiratory tract due to the irritant/corrosive nature of C(M)IT/MIT. It is proposed to adopt the classification Xn; R20 ‘Harmful by inhalation” based on the studies from Dow and Thor (corr. to T+;R26 ‘Very toxic by inhalation’ for C(M)IT/MIT 3:1) according to the directive 67/548/EC. A classification as Acute Tox 4 / H332: Harmful if inhaled is required according to the regulation 1272/2008/EC (corr. to Acute tox 2 / H 330: Fatal if inhaled for C(M)IT/MIT 3:1).

The major metabolite of C(M)IT/MIT, NMMA, did not produce clinical toxicological signs in a 14-day rat study up to 2500 mg/kg bw, giving a LD50 of 3550 mg/kg bw in males and 4100 mg/kg bw in females. Clinical toxicological signs (decreased respiration, piloerection, ataxia and CNS depression) were observed at 5000 mg/kg bw and congestion, hemorrhagic type responses and gastro-intestinal irritation were observed in dead from the 2500 mg/kg dose group.

Justification for classification or non-classification

Classification is justified on the basis of results obtained in well conducted, guideline compliant, oral, dermal or inhalation acute toxicity studies.