ε-caprolactam

Endpoint summary

Description of key information

No valid animal data available, classification as an irritant on all relevant routes of exposure based on human experience. 

Additional information

Skin/eye irritation:

No valid animal data is available for Caprolactam (CAP) with regard to skin and eye irritation.

The most valuable animal skin irritation study is a range finding study of a skin sensitization test in which 0.4ml of a 75% CAP-solution were applied to the clipped skin of guinea pigs (Springborn, 1991). 24h following a 6h occlusive incubation period mild signs of irritation were observed which decreased after a further 24h observation period. Therefore mild skin irritation can not be ruled out, though due to significant deviations to the OECD guideline 404 no classification according to EU- or GHS-standards can be performed.

In an acute dermal assay application of 2000mg/kg bw on an undefined area of rat skin did not result in local signs of irritation (Bayer, 1987).

No valid study to approximate the potential to irritate mucosa is available.

 

Respiratory irritation:

In an inhalation study with mice (Alarie test, Industrial Health Foundation, 1990), pulmonary irritation of CAP was studied by exposing groups of 4 guinea pigs for 30 min/day on 5 consecutive days to 3 aerosol concentrations (0.003, 0.01 and 0.03 mg/l). There was no change in respiratory frequency (f) or amplitude (AP). Following inhalation exposure the breathing patterns remained unaltered (i.e., no sensory or pulmonary irritation) and there was no evidence of airway constriction.

 

In a further inhalation study (Dupont, 1997), groups of 4 male mice were exposed for 30 min to saturated vapors of CAP (0.0094 mg/l) and evaluated for sensory irritation. A decrease in respiratory frequency of 8% was observed, which is generally considered within the expected range for control mice exposed to air in this system. However, during this exposure there was some evidence of slight sensory irritation observed in 1 of 3 mice.

 

Human experience:

In man the solid substance and concentrated solutions were reported to be local irritants (e.g. Brief, 1971; Antoniev & Gerasimow, 1971) and in some reports high concentrations of the dust were irritant to mucous membranes (e.g. Tuma et al., 1981; Reinhold et al. 1998).

Eye irritation, burning nostril, irritation of the throat and coughing were observed in most of the healthy human volunteers exposed to artificially generated CAP vapors (10-104 ppm,and Wheeler, 1973).

 

In low atmospheric concentrations CAP is existent as a vapor, whereas in higher concentrations increased aerosol formation occurs due to the low vapor pressure.

In order to study the chemosensory effects on the conjunctiva or nasal mucosa at low concentrations below the MAK value, Ziegler et al. (2008) exposed 20 healthy subjects (10 male, 10 female) for 6 h exposures to vaporous CAP in the concentrations of 0, 0.15, 0.5 and 5 mg/m3. Indications for an increases in blink frequency, nasal resistance and irritation were reported in the highest test concentration (5 mg/m3), although not to statistically significant degree and therefore not adverse. Also the subjective indications of symptoms increased statistically insignificant with rising levels of exposure. Only odor nuisance was significantly more pronounced than at zero exposure (P < 0.001) even in the low concentration range.

 

Kelman (1986) reported minor complaints of sensory irritation and peeling and/or fissuring of the skin in a group of eight workers exposed to CAP fume/dust levels of 68 mg/m3 (range 22-168 mg/m3) for 9 months to 13 years. At mean concentration of 61 mg/m3 CAP vapor workmen in spinning rooms reported dry, splitting nose and lips, noose bleed and upper respiratory catarrh (Hohensee, 1951).

 

The maximum allowable concentration at the workplace (German MAK value) is defined as the maximum concentration of a chemical substance in the workplace air which generally does not have known adverse effects on the health of the employee and does not cause unreasonable annoyance even when the person is repeatedly exposed during long periods, usually for 8 hours daily but assuming on average a 40-hour working week (DFG, 2005). For CAP the MAK value was identified as 5 mg/m³, corresponding with the U.S. Threshold Limit Value (TLV; ACGIH, 2004). Both values were in principle established on the basis of its known irritant effects on man (mucosal, skin or chemosensory irritation). 

Accordingly, classification and labeling should reflect the observed irritating effects of CAP to the skin, eyes and respiratory tract according to EU (R38, R36, R37) and GHS (Cat 2, Cat 2, STOT acute Cat 3) standards.

Justification for classification or non-classification

No valid animal data available, classification as an irritant on all relevant routes of exposure based on human experience.