Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.001 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
Overall assessment factor (AF):
25 000
Modified dose descriptor starting point:
T25
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

DNEL acute/short-term exposure, systemic effects:

A DNELacuteshould be established for substances if an acute hazard toxicity (leading to C&L) has been identifiedanda potential for high peak exposures exists.

The substance is classified as very toxic after oral, dermal and inhalation exposure. However, as there is no potential for high peak exposures, acute DNELs do not need to be established.

 

DNEL short-term/long-term exposure, local effects:

Ethylenimine is classified as corrosive (Classification according to Directive 67/548/ EEC: corrosive, R34; classification according to CLP (Directive 1272/2008): Skin corrosion Category 1 and Serious eye damage/eye irritation Category 1). The corresponding in vivo skin and eye irritation/corrosion tests were performed at one dose level. Therefore, the tests do not provide dose-response data that could be used for the derivation of a DNEL. Also, no quantitative human data on skin corrosion and eye damage (concentration) were available. Furthermore, as no exposure is expected due to the highly accepted use of suitable personal protective equipment and as it can be assumed that, as a rule, daily repeated immediate skin contact is avoided to a large extent by using suitable personal protective equipment, a DNEL has not been derived.

 

 

DMEL long-term exposure, systemic effects:

As ethylenimine is classified as carcinogenic and showed tumour development in a carcinogenicity study in rats, a long-term DMEL has to be established. In this hazard evaluation, the key study to be used to determine the chemical’s hazard is an one-year inhalation carcinogenicity study in rats (BASF AG, 1978). This study provides a sound basis for determining the hazard of ethylenimine.

The most significant effect was considered to be the development of uterus/vagina sarcomas. Based on this effect and its incidence, the T25 was determined to be 17.8 mg/m3.

 

Therefore, the inhalation DMEL for long-term exposure - systemic effects for workers has been derived as follows:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

T25: 17.8 mg/m3

 Incidence of uterus/vagina sarcomas (BASF AG, 1978)

Step 2) Modification of starting point

1.5

 

 

 

0.67

Correction for difference in exposure time (6 h/8 h x 5 d/5 d x 52 w/48 w x 75 y/40 y)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling has to be applied as an inhalation study is used as starting point (concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and human are to be taken into account).

Intraspecies

1

No assessment factor applied because of the non-threshold effect (mutagenic & carcinogenic).

Exposure duration

1

Already corrected for under step 2.

Dose response

1

 

Quality of database

1

 

Risk level to be estimated

25000

For workers 10-5

DMEL

Value

For workers

(17.8 mg/m³ x 1.5 x 0.67) / (1 x 1 x 1 x 1 x 1 x 25000) =0.000716 mg/m3(approx. 0.001 mg/m³)

 

 

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Exposure to the general population is not expected, and therefore a DNEL and/or DMEL has not been established.