N-(1-oxooctyl)glycine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.57 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

DNEL related information

Overall assessment factor (AF):

225

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

75

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.222 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

DNEL related information

Overall assessment factor (AF):

900

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.667 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

NOAEL

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Workers

No assessment and notably no DNEL is required for the general public because:

 

-   the latter is only exposed via the use of final cosmetic products, excluded from the CSA;1

 

-   assessment of indirect human exposure via the environment is not required, since thesubstance does not require classification as “T/R48”, as a carcinogen or mutagen (of any category), or as toxic to reproduction (category 1 or 2).

 

No DNEL is required for oral exposure of workers since no significant exposure occurs by this route for trained workers (who do not smoke, eat or drink when manipulating chemicals).

 

No DNELs are required for acute toxic effects, sensitization and skin irritation because the substance does not possess these properties and long-term DNELs are sufficient to cover systemic effects, as a worst-case. Furthermore most of these DNELs can not be calculated with the available qualitative or single-dose data.

 

No DNEL for eye irritation can be derived as the corresponding test is qualitative.

 

No additional assessment factor for route-to-route extrapolation has been used when deriving dermal and inhalation DNELs from data obtained in oral studies. Indeed, the dermal absorption by oral route (solubilised ground substance given by gavage in the study under section 5.6.1.1 of the CSR; expected good oral absorption as discussed under section 5.1of the CSR) is considered to be at least as high as absorption by dermal and respiratory routes (two routes by which absorption is probably not null but of undetermined extent, as discussed under section 5.1of the CSR).

 

An additional assessment factor of 3 has been used to derive the developmental DNEL because of the limited extent of pup examinations in OECD 422 vs. OECD 414

For the dermal route, oral an assessment factor of 900 is applied and is justified as followed:

No additional assessment factor for route-to-route extrapolation has been used when deriving dermal and inhalation DNELs from data obtained in oral studies. Indeed, the dermal absorption by oral route is considered to be at least as high as absorption by dermal and respiratory routes (2 routes by which absorption is expected to be virtually null). The oral route is therefore an extreme worst-case situation in terms of absorption and the DNELs derived from oral data can be considered as being very conservative.

- interspecies, allometric scaling factor =1

Assessment factors(worker)

- Interspecies = 4*2.5 = 10

- Intraspecies: 5

- Exposure duration sub-acute (28 days to chronic) = 6

- Reliability of the dose-response data = 1 (NOAELs availables, no severe effect)

- Quality of the complete endpoint-specific database = 1 for repeated dose toxicity and fertility; 3 for developmental toxicity

- Overall assessment factors: 300 for repeated dose toxicity and fertility; 900 for developmental toxicity

=>DNEL = 200/900 = 0.222 mg/kg/d

For the inhalation route, an assessment factor of 225 is applied and is justified as followed:

For route-to-route extrapolation, the calculation approach follows the Guidelines predefined (see R:8-2).

-Corresponded volume for relevant duration: Worker: 10 m3 (8hours light work)

=>NOEC (worker, 8 h) = 200 x 1/0.38 x 6.7/10 = 353 mg/m3

Assessment factors(worker)

- Interspecies, remaining differences= 2.5

-Intraspecies = 5

- Exposure duration subacute (28 days) to chronic = 6

- Reliability of the dose-response data = 1 (NOAELs availables, no severe effect)

- Quality of the complete endpoint-specific database = 1 for repeated dose toxicity and fertility; 3 for developmental toxicity

Overall assessment factors: 75 for repeated dose toxicity and fertility; 225 for developmental toxicity

=>DNEL = 353/225 = 1.57 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

General population

No assessment and notably no DNEL is required for the general public, as the latter is only exposed to the substance via the use of final cosmetic products. Assessment of human health effects for such exposure is not required by REACH.