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Description of key information

CAP is harmful if swallowed and if inhaled according to EU (R22, 20) and GHS (acute oral/inhal Cat. 4) standards. No signs of systemic toxicity.
LD50 Oral (rat) = 1475 mg/kg bw (male) and 1876 mg/kg bw (female)
LD50 Dermal = >2000 mg/kg bw (rat)
LC50 Inhalation-aerosol (rat) = 8.16 mg/l (male/female) with 1 of 10 dead animals at limit dose of approx 5 mg/l.

Key value for chemical safety assessment

Additional information

Oral exposure route:

In the key study (Bayer, 1987) performed according to guideline and GLP, the LD50 for male and female rats was reported to be 1475 and 1876 mg/kg bw, respectively. Significant mortality was observed from the dose level of 1600 mg/kg bw within 6 h after exposure. Clinical signs were clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were persistent until the end of the 7 days observation period. At necropsy, redness in the lungs and gastro-intestinal tract, and enlarged liver were described.

These findings were supported by further acute oral studies in which LD50 values of 1650 and 1210 mg/kg bw for male and female rats, respectively (NTP, 1982), and 1660 mg/kg bw (BASF AG, 1965) were reported. Both studies also supported the finding of caprolactam being a convulsant poison when applied in high oral doses.

Regarding acute oral toxicity in further species, LD50 values in the range of 300-1000 mg/kg bw were reported for rabbits and cats (BASF AG, 1965) and 2070 and 2490 mg/kg bw for male and female mice, respectively (NTP, 1982).

In addition, few studies with limited documentation (Reliability 4) reported LD50 values of 1155 mg/kg bw (Bornmann, 1959) and 3375 mg/kg bw (Dupont 1950) in rats, 1200 mg/kg bw in mice (Hohensee, 1959), and 1000 mg/kg bw in rabbit and mice (Lomonova, 1986).

Taking all the presented data into consideration, CAP is classified as "harmful if swallowed" according to EU (R22) and GHS (Cat. 4) standards.

 

Dermal exposure route:

The key study is a limit dose test with rats performed according to guideline with GLP (Bayer, 1987). 24 h o dermal exposure to 2000 mg/kg bw under occlusive conditions resulted in no mortalities or signs of toxicity.

Further studies of limited reporting and experimental quality were identified in the database:

for rabbits LD50 values of 3375 mg/kg (DuPont, 1950) and 1520 mg/kg bw were reported (occlusive exposure for 24 h, Smyth et al., 1969).

Thus CAP does not require any classification.

 

Inhalation exposure route:

In the key study performed similar to the guideline 403, rats were exposed to a liquid aerosol of the test substance using a head-nose inhalation system at analytical concentrations of 5.25, 8.35 and 10.12 mg/l for 4 hours (BASF AG, 1985). Exposure related mortalities were observed at all dose levels and the LC50 for male/female was determined to be 8.16 mg/l.

Observed clinical signs of toxicity were indicative for irritation (eyelid closure, irregular respiration, escape reaction during exposure and dyspnoea, piloerection, bloody nose and eye discharge and tremor after exposure). Clinical signs were reversible with 7 days post exposure.

The LC50 is above 5 mg/l but 1/10 animals died at this limit concentration and clinical signs of irritation were observed. Based on the LC50 of 8.16 mg/L for male/female rats (aerosol), no classification is required according to 67/548/EEC Directive (annex VI) criteria and according to CLP (annexe I) criteria. However, caprolactam is officially classified as Xi, R20 and as acute tox. Category 4 (H332: harmful if inhaled) according to CLP regulation annex VI table 3.2 and 3.1. This official classification is finally taken in to account.

Experimental quality and reporting of all further acute inhalation experiments was insufficient. LC50 values of 0.45 mg/l (Lomonova, 1961) or >2.98 mg/l (DuPont, 1950) were reported for the aerosol in mice or rats, respectively. But no analysis of the exposure atmosphere was performed and various undefined exposure equipments and times were chosen.

One experiment is addressing the toxicity of a saturated vapor concentration of CAP (0.0061 mg/l) in mice. Minimal signs of sensory irritation were reported (DuPont, 1997). 

Justification for classification or non-classification

CAP is harmful if swallowed and if inhaled according to EU (R22, 20) and GHS (acute oral/inhal Cat. 4) standards. No signs of systemic toxicity.