Registration Dossier

Administrative data

Description of key information

NOAEC (systemic): 8117 mg/m³

Key value for chemical safety assessment

Additional information


Similar to OECD 413, varnish makers' and painters' naphtha was administered via whole body inhalation to male rats at concentrations of 0, 280, 600, and 1200 ppm for 6 hours/day, 5 days/week, for 13 weeks (Carpenter et al., 1975a). Two rats in the 280 ppm group died of lung abscesses and pneumonia on the 9th and 65th days of exposure. No other deaths or clinical signs of distress were observed at any other concentration; therefore, these deaths were not considered toxicologically significant. At 1200 ppm, statistically significant increases in neutrophils and decreased leukocyte counts were observed in rats sacrificed after 8 weeks. These effects were within normal range and were not seen in rats at 13 weeks, however statistically significant decreased erythrocytes were seen at this concentration. No statistically significant variations between controls and any treated group were observed for clinical chemistry or body weight changes. Some tubular regeneration in the kidneys of all rats (control and treated groups) was observed but was not progressive with concentration or duration of exposure and was not considered of pathological significance.The NOAEC was estimated to be 5800 mg/m³ corresponding to 1200 ppm.

In a similar study described above, four male dogs/concentration were exposed to varnish makers' and painters' naphtha via whole body inhalation at concentrations of 0, 280, 600, and 1200 ppm for 6 hours/day, 5 days/week, for 13 weeks (Carpenter et al., 1975b). All dogs survived exposure. Statistically significant increase in serum alkaline phosphatase levels was observed at 1200 ppm compared to concurrent control and predose values. A slight but statistically significant increase in relative liver weights was seen in the 600 ppm dogs; absolute weights were comparable to controls. No adverse effects were observed for body weight changes in 5800 and 1300 mg/m³ groups, food consumption, electrocardiograms, urinalysis, hematology, other clinical chemistry parameters, or histopathology. Based on the alkaline phosphatase changes, the NOAEC was 2800 mg/m³ corresponding to 600 ppm.

The fact, that the study of Carpenter et al. (1975a) used only male rats of which two died of pneumonia, and that tubular regeneration in the kidneys was observed in treated and control rats, the NOAEC of 5800mg/m³ based on statistically significant decreased erythrocytes is questionable since it is not clear whether the effect is exposure related. In the inhalation study of Carpenter et al. (1975b) dogs, which are not the relevant species, were used. Therefore, additional experimental data were used to evaluate repeated dose toxicity via inhalation.

There are reliable data available for the structurally related substance light alkylate naphtha distillate. Thus, read-across was conducted based on a structural analogue.

A 13-week inhalation toxicity study was conducted using wholly vaporized light alkylate naphtha distillate (LAND-2) generated in nitrogen (Schreiner et al., 1998). Male and female rats were exposed by inhalation in whole-body exposure cages 6 hours/day, 5 days/week for 13 weeks at analytical concentrations of 0, 668, 2220, and 6646 ppm. All animals survived the treatment period and were sacrificed according to study design at the end of week 13 or 18 (recovery group). No test-related observations were noted in the exposure chambers during any exposure period for any treatment groups or during non-exposure periods. From weekly clinical observations, the only apparent treatment-related finding was an increased incidence of red facial staining in both male and female rats in the high dose group. At week 13, there were statistically significant dose-related increases in absolute and relative kidney weights in males of all 3 treatment groups. The kidney weights of high-dose males remained elevated after the recovery period. These increases correlated with microscopic observations of hyaline droplet formation in the proximal convoluted tubules considered to contain an alpha2-microglobulin-hydrocarbon complex as well as an increase in incidence and severity of nephropathy and dilated tubules at the corticomedullary junction. These microscopic finding are characteristic of ‘light hydrocarbon nephropathy” also known as hyaline droplet nephropathy and are male rat specific. Therefore these effects are not considered to be relevant to humans. Statistically significant increases in absolute and relative liver weights were observed in high-dose male and female rats at week 13 after sacrifice. Differences were not present after the recovery period and had no microscopic correlate. Thus, the NOAEC for systemic toxicity was 8117 mg/m³ corresponding to 2200 ppm.

The NOAEC of the inhalation study of Schreiner et al. (1998) conducted with light alkylate naphtha distillate was taken in order to evaluate the risk potential of the registered substance hydrocarbons, C7-C8, n-alkanes.

Justification for classification or non-classification

Based on read-across from a structurally related substance (light alkylate naphtha distillate), no inhalation repeated dose toxicity is expected from the exposure to the registered substance hydrocarbons, C7-C8, n-alkanes. No need for classification according to the DSD and CLP criteria for classification and labelling.