Registration Dossier
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EC number: 236-740-8 | CAS number: 13472-08-7
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.705 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 17.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 10 mg/kg/day from an OECD 408 oral study with rats on a read-across substance was used. Assuming an oral/inhalation absorption of 1.0, a dose descriptor of 17.6 mg/m3 was derived as the starting point.
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA guidance
- AF for differences in duration of exposure:
- 2
- Justification:
- In accordance with ECHA guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In accordance with ECHA guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA guidance
- AF for intraspecies differences:
- 5
- Justification:
- In accordance with ECHA guidance
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA guidance
- AF for remaining uncertainties:
- 1
- Justification:
- In accordance with ECHA guidance
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 970.87 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 97 087 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 10 mg/kg/day from an OECD 408 oral study with rats on a read-across substance was used. A dermal penetration study is available. The mean penetrated amount is 0.0103% of applied dose on human skin. Therefore 10 mg/kg/day/0.000103 results in a dose descriptor of 97087 as the starting point.
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA guidance
- AF for differences in duration of exposure:
- 2
- Justification:
- In accordance with ECHA guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- In accordance with ECHA guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA guidance
- AF for intraspecies differences:
- 5
- Justification:
- In accordance with ECHA guidance
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA guidance
- AF for remaining uncertainties:
- 1
- Justification:
- In accordance with ECHA guidance
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
CAS# 13472 -08 -7 DNEL Discussion Revised 4-17-2017
The DNELs for the registered substance were calculated using the results from an OECD 408 study conducted with the read-across substance, 2,2’-azodi(isobutyronitrile) CAS# 78-67-1.
In conclusion, daily administration of the read-across substance for 13 weeks at dose levels of 0.5, 2 or 10 mg/kg/day was well tolerated. There was no evidence of neurotoxicity. There were slight changes in some blood clinical chemistry and urine parameters at all dose levels. The liver and kidney were identified as target organs based on increased weights (at all dose levels in males) and
microscopic findings of hepatocyte hypertrophy (at all dose levels in males and at =2 mg/kg/day in females) and focal nephropathy/tubular basophilia and hyaline droplets in males at all dose
levels. The liver hypertrophy is considered an adaptive change commonly associated with metabolic burden and the changes in the kidney are considered specific to the male rat as
confirmed by immunohistochemical staining. Therefore, the nature of these histopathological changes are considered to be of no toxicological relevance and the No-Observed-Adverse-Effect-
Level (NOAEL) is considered to be 10 mg/kg/day.
Systemic Dermal DNEL Worker
A systemic NOAEL of 10 mg/kg/day is based on the OECD 408 oral rat gavage study.
Oral absorption rat — oral/dermal absorption human: A dermal penetration study is available. The mean penetrated amount is 0.0103%of applied dose on human skin.
= 10 mg/kg bw/day/0.000103
= 97,087 mg/kg bw/day dermal dose descriptor
Correction for interspecies differences (apply factor for allometric scaling 4 for rat x 2.5 for additional factors):10
= 97087 mg/kg bw/day / 10
= 9708.7 mg/kg bw/day
Correction for intraspecies differences: 5
= 9708.7 mg/kg bw/day / 5
= 1941.7 mg/kg bw/day
Correction for duration between 90 day exposure to chronic: 2
= 1941.7 mg/kg bw/day / 2
= 970.87 mg/kg bw/day
Correction for dose-response: 1
= 970.87 mg/kg bw/day / 1
= 970.87 mg/kg bw/day
Correction of whole database: 1 due to quality of study
= 970.87 mg/kg bw/day / 1
= 970.87 mg/kg bw/day (DNEL dermal-worker-systemic)
based on an overall AF of 100
Systemic Inhalation DNEL Workers
Corrected inhalation NOAEC from oral NOAEL
oral NOAEL x (1/sRVrat)x(ABSoral-rat/ABSinh-human)xs(RVhuman/wRV)
ABSoral-rat/ABSinh-human is 100/100 = 1.0 Due to the low volatility and high water solubility, the respiratory absorption and oral absorption were considered equal. Guidance on requirements and chemical safety assessment Ch. R.7c pg 159 state that, “Vapors of very hydrophilic substances may be retained within the mucus. For absorption of deposited material similar criteria as for GI absorption apply.”
= 10 mg/kg bw/day x (1/0.38m3/kg bw/day) x (1.0) x (6.7m3/10m3)
= 17.621 mg/m3inhalation dose descriptor
[: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume]
Additional correction for interspecies differences: 2.5
= 17.621 mg/m3/2.5
= 7.048 mg/m3
Correction for intraspecies differences: 5
= 7.048 mg/m3/ 5
= 1.41 mg/m3
Correction for duration between 90 day exposure to chronic: 2
= 1.41 rng/m3/ 2
= 0.705 mg/m3
Correction for dose-response: 1
= 0.705 mg/m3/ 1
= 0.705 mg/m3
Correction of whole database: 1 due to quality of study
= 0.705 mg/m3/1
= 0.705 mg/m3(DNELinhalation-worker-systemic)
based on an overall AF of 25
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - 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.
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