Ethylene chlorohydrin




Home ContactUs 中文 English
Yourlocation:Home >News> Chlorohydrin data analysis for aegl-3

Chlorohydrin data analysis for aegl-3

Time:2015/9/24 7:22:49

chlorohydrin human data relevant to aegl-3

reports of human deaths following occupational exposure accidents lack definitive exposure terms. estimated exposures of 300 ppm for approximately 2 hours and at 500 ppm

(unknown duration) were reportedly lethal.

chlorohydrin animal data relevant to aegl-3

exposures as low as 1120 ppm for 30 minutes (rats) and 1260 ppm for 30 minutes (mice) caused 100% lethality (goldblatt, 1944). results from this study also showed that exposure of rats to 840 ppm for 15 minutes or of mice to 280 ppm for 120 minutes was not lethal. the study was compromised by the small number of animals used (3 per group). although the animal data do not precisely describe the exposure-response relationship for inhalation exposure to ethylene chlorohydrin vapor, the data do differentiate between nonlethal and lethal exposures.

chlorohydrin derivation of aegl-3 values

data are unavailable with which to definitively assess the exposure-response relationship for lethality resulting from inhalation exposure to ethylene chlorohydrin. experiments in animals are compromised by small numbers of animals per exposure group and by response data showing near 100% lethality or no lethality. these data do not allow for a valid estimation of a lethality threshold using benchmark dose (u.s. epa, 2007) methodologies. therefore, exposure data from the goldblatt (1944) report showing no lethality were considered as estimates of a lethality threshold for aegl-3 development. the data in mice provided both a nonlethal (280 ppm) and 100% lethality (1090 ppm) for the same exposure duration (120 minutes) and, therefore, were considered most appropriate as a point-of-departure (pod) for aegl-3 derivation.

empirical derivation of a temporal scaling factor (n) is not possible with the available data. the exposure concentration-exposure duration relationship for many irritant and

systemically acting vapors and gases may be described by cn 35 x t = k, where the exponent, n,ranges from 0.8 to 3.5 (ten berge et al., 1986). in the absence of an empirically derived exponent (n), temporal scaling from the experimental durations of the respective pods to aegl-specific durations was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the cn 39 x t = k equation.

although the animal data identify only nonlethal or lethal responses, comparison of the exposure-response data indicated less than a 3-fold difference between rats and mice (table 5).

limited data in guinea pigs suggested this species to be less sensitive than the rats and mice. based upon the differences in the lethal response between the more sensitive rats and mice, an ethylene chlorohydrin (2-chloroethanol) page 18 of 37 interim 05/2008 interspecies uncertainty factor of 3 was considered appropriate. ethylene chlorohydrin does not appear to be a direct-contact irritant and death in animals does not appear to be a function of damaged respiratory tract epithelial tissue. in the absence of data regarding the mode of action of ethylene chlorohydrin toxicity and because of the small numbers of animals used in the reported studies, an intraspecies uncertainty factor of 10 is retained. the total uncertainty factor adjustment is 30. the resulting aegl-3 values are shown in table 8 and their derivation summarized in appendix a. a comparison of the aegl-3 values to the human lethality (estimated as 300 ppm for 2 hours) reported by dierker and brown (1944) shows the aegl-3 values as sufficiently protective (protection of sensitive populations would necessitate an order of magnitude reduction of the 300 ppm exposure to 30 ppm) and serves to justify the interspecies uncertainty factor.