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EC number: 250-418-4
CAS number: 30989-05-0
The following parameters were taken into account for the modification of the dose descriptor starting point:
modifed NOAEC (worker, 8h inhalation) = NOAEL (oral, rat) * [1/sRV(rat, 8h)] * [ABS (oral) / ABS (inhalation)] * [sRV (human) / worker Respiratory Volume (wRV)] * [7d (per week) / 5d (per week)]
modified NOAEC (worker, 8h inhalation) = 300 mg/kg bw/d * [1/0.38 m³/kg bw/d] * [0.5 / 1] * [6.7 m³ (8h) / 10 m³ (8h)] * [7d (per week) / 5d (per week)] = 370.3 mg/m³
modified NOAEL (worker, dermal) = NOAEL (oral, rat) * [ABS (oral) / ABS (dermal)] * [7d (per week) / 5d (per week)]
modified NOAEL (worker, dermal) = 300 mg/kg bw/d * [1 / 1] * [7d (per week) / 5d (per week)] = 420 mg/kg bw/d
Long-term DNELs for systemic effects are based on the key oral extended one-generation reproductive toxicity study (according to OECD 443), in which the test item B-TEGME was administered by oral gavage to Sprague-Dawley rats at dose levels of 100, 300 and 1000 mg/kg bw/day.
Based on the results obtained in this study it was concluded that the No-Observed-Adverse-Effect-Level (NOAEL) for reproductive performance of the F0 and F1 Cohort 1B animals was 300 mg/kg/day due to the high incidences of reduced fertility in females of F1 Cohort 1B receiving 1000 mg/kg/day and the increased incidences of minimal epididymal cellular debris coupled with sperm motility and morphology changes in both F0 and F1 Cohort 1B males given 1000 mg/kg/day, accompanied with degeneration in the testes for F1 Cohort 1B males at 1000 mg/kg/day only.
Aside from the above-mentioned instances of reduced fertility and male reproductive system changes at 1000 mg/kg/day, increased incidences of basophilic tubules in the kidneys of F0 females and increased incidence of decreased lymphocytes in the cortex of the thymus in the F0 generation males were observed at 1000 mg/kg/day, therefore the NOAEL for systemic toxicity in the F0 and F1 adult animals was concluded to be 300 mg/kg/day.
The NOAEL for the F1 and F2 offspring up to weaning was concluded to be 300 mg/kg/day due to reduced early post-partum survival at 1000 mg/kg/day in both generations and low litter size in F2 litters.
There was no evidence of developmental neurotoxicity or developmental immunotoxicity on this study, therefore the NOAEL for these endpoints was concluded to be 1000 mg/kg/day.
For the derivation of DNELs, the ECHA Guidance on IR&CSA, Chapter R.8, was followed, and ECHA default assessment factors were considered to be appropriate for workers.
modifed NOAEC (general population, 24h inhalation) = NOAEL (oral, rat) * [1/sRV(rat, 24h)] * [ABS (oral) / ABS (inhalation)]
modified NOAEC (general population, 24h inhalation) = 300 mg/kg bw/d * [1/1.15 m³/kg bw/d] * [0.5 / 1] = 130.4 mg/m³
modifed NOAEL (general population, dermal) = NOAEL (oral, rat) * [ABS (oral) / ABS (dermal)]
modified NOAEC (general population, dermal) = 300 mg/kg bw/d * [1 / 1] = 300 mg/kg bw/d
The modification of the NOAEL is not
necessary as no route-to-route extrapolation is performed.
The detailed information of the study and dose descriptor used as point of departure for the derivation of long-term DNELs is described in 'additional information - worker' above.
For the DNELs, the ECHA Guidance on IR&CSA, Chapter R.8, was followed, and ECHA default assessment factors were considered to be appropriate for the general population.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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