Benzylmagnesium chloride

Endpoint summary

Additional information

At the present time, no data about repeated dose toxicity endpoint are available for the substance as described in section 1.2. For this reason, some scientific evidence of toxicity under repeated administration of tetrahydrofuran (stabilizaer additive of benzylmagnesium chloride) were assessed.

In the NTP 1998 study, 10 male and 10 female rats have been exposed to 0, 66, 200, 600, 1800, 5000 tetrahydrofuran inhalation for 14 weeks, 5 days per week. Immediately after exposure, rats in the 5000 ppm group exhibited ataxia, with irregular movements and lack of coordination. Hematology and clinical chemistry data differences between exposure groups did not demonstrate a strong exposure relationship and only occurred in the 5000 ppm group. However, these data were not toxicologically relevant. The decrease of thymus and spleen weights were not associated with readly appreciable histopathological changes and may have been due to stress associated with tetrahydrofuran administration.

Furthermore, 10 male and 10 female mice have been exposed to 0 (chamber controls), 66, 200, 600, 1800, 5000 tetrahydrofuran inhalation for 14 weeks, 5 days per week. Two male mice exposed to 5000 ppm died during week 2 and 8 of the study; one male mouse of the same exposure level was killed in a moribund state during week 4. All female mice survived until the end of the study. The final mean body weights and body weight gains of all exposed group of male mice were similar to those of the chamber controls. The final mean body weights and body weight gains of female mice exposed to 5000 ppm were significantly greater than those of the chamber controls. Mice exposed to 1800 or 5000 ppm were observed in a state of narcosis during exposure period. Mice exposed to 1800 ppm recovered immediately after exposure, while 5000 ppm exposed mice required up to 2 hours for recovery. Absolute and relative liver weights of male mice exposed to 600 ppm or greater and of female mice exposed to 1800 or 5000 ppm were significantly greater than those of the chamber controls. Absolute and relative lung and heart weights of female mice exposed to 5000 ppm were significantly less than those of the chamber controls. Absolute and relative thymus weights of male mice exposed to 600, 1800 or 5000 ppm were significantlly less than those of the chamber controls. Absolute and relative spleen weights of male and female mice exposed to 5000 ppm were significantly less tha those of the chamber controls. Although there were decrease in thymus and spleen weights, corresponding histopatologic changes were not readly appreciable. However, the spleens of male and female mice exposed to 5000 ppm had smaller cross sections. The significance of these organ weight differences is not clear, but the differences may be due to stress associated with tetrahydrofuran exposure. No exposure-related gross lesions were observed in male and female mice at necropsy.The adrenal glands of all female mice exposed to 5000 ppm had mild degeneration of the X-zone of the innermost cortex. Furthermore, uterine atrophy, characterized grossly by small by small uteri and microscopically by fewer numbers of uterine glands, was observed in all female mice of the 5000 ppm group. However, it is not known whether adrenal gland X-zone degeneration or utherine atrophy represented an acceleration of normal aging changes due to a hormonal effect or an organ-specific, exposure-related, target-organ effect.

In an additional study groups of male and female rats Crl:CD BR received tetrahydrofuran inhalation exposure at concentrations of 0, 500, 1500 and 5000 ppm.

This study indicates that the principal neurobehavioral effect of exposure to 1500 ppm and greater concentrations of THF is acute behavioral sedation which dissipates rapidly upon termination of exposure. These results are consistent with reports of occupational over exposure in which transient effects on the central nervous system were noted. There was no evidence that subchronic exposure caused enduring adverse effects on nervous system structure or function. For neurobehavioral end points, the no-observed-effect level for THF in subchronic exposure scenarios was 500 ppm, based on concentration-dependent findings of acute and transient behavioral sedation with single or repeated exposure to 1500 or 5000 ppm.

Justification for classification or non-classification

At the present time, no data about repeated dose toxicity endpoint are available for the substance as described in section 1.2. For this reason, some scientific evidence of toxicity under repeated administration of tetrahydrofuran (stabilizer additive of benzylmagnesium chloride) were assessed.

No definitive scientific evidence of the onset of repeated dose related damage on target organ from tetrahydrofuran administration by inhalation route on mice and rats has arisen as described by related end-points records. For this reason and for the fact that no direct data for benzylmagnesium chloride with THF as stabilizer additive (as described in sect. 1.2) are available, it's not possible to classify this substance under CLP and DSD for this specific end-point.