1,1-difluoroethylene

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 045 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

Modified dose descriptor starting point:

NOAEC

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

Additional information - workers

According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

As the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes.

 

As the substance is not classified for acute toxicity, according to the REACH “Guidance on information requirements and chemical safety assessment” (R.8.4.3.1), no acute / short-term exposure DNELs need to be derived.

 

For long-term exposure, data from subchronic (13 weeks/90 days) and combined chronic toxicity/carcinogenicity (104 weeks) studies with rats and mice are available. In the 13 week studies, no target organs were consistently identified.

In the combined chronic toxicity/carcinogenicity studies no adverse effects were observed at the highest concentration tested (10000 ppm (26000 mg/m³)).

In this hazard evaluation, the primary studies for DNEL derivation are the chronic toxicity/carcinogenicity studies (TNO (1991) and Bio/dynamics Inc. (1991)). They are preferred above the well-conducted 2 weeks and 13 weeks/90 days studies of Bio/dynamics Inc. (1988; 1989) based on the study duration (chronic vs. semichronic/subacute). They are also preferred above the male/female fertility study in which no effects were observed up to the highest concentration tested (7000 ppm (18000 mg/m³)). As in this fertility study animals were exposed up to 18 weeks and limited histopathology has been performed (study focus was on fertility parameters, not on general toxicity parameters after chronic exposure), this study is not considered as the key study for DNEL derivation.

The two chronic key studies were performed according to currently accepted guidelines and GLP standards. It is believed that the overall quality, detailed description and length of the studies, provides a sound basis for determining the hazard of vinylidene fluoride. Many of the subchronic studies do not have the level of detail provided in the more recent GLP chronic studies. In addition, many of the effects observed in the subchronic studies were not considered to be dose related or transient and in many cases not related to organ pathology. The overall weight of evidence regarding the studies and the inability to reproduce the same effects in the chronic GLP studies should also be taken into consideration.

In conclusion, the NOAEL (10000 ppm (26000 mg/m³) from the chronic toxicity studies is selected for DNEL derivation for systemic effects.

 

As no local effects were observed in the long-term inhalation exposure studies, no DNEL for local effects was derived.

 

The DNEL for long-term inhalation exposure - systemic effects for workers is derived as follows:

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL:26000mg/m^3	The highest dose concentration in the combined chronic toxicity/carcinogenicity study with rats; no adverse effects observed
Step 2) Modification of starting point	6/8 6.7 m^3/10 m^3	Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);   Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m^3/10 m^3).
Step 3) Assessment factors
Interspecies	2.5	For inhalation studies only a factor 2.5 is used, and no correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements.
Intraspecies	5	A default assessment factor for workers, as proposed in the REACH Guidance (R.8.4.3.1)
Exposure duration	1	No extrapolation of exposure duration is required, as the NOAEL is from a chronic study
Dose response	1
Quality of database	1
DNEL	Value
For workers	26000 x 6/8 x 6.7/10 / (2.5 x 5 x 1 x 1 x 1) =1045 mg/m^3

  The worker DNEL value derived for chronic inhalation would have to be adapted  in case of a different  shift system (= daily exposure time). In that case the amended DNEL would results in virtually the same value under the condition that the weekly exposure time would be almost identical.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

260 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

25

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

Additional information - General Population

 The DNEL for long-term inhalation exposure - systemic effects for the general population is derived as follows:

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 26000mg/m^3	The highest concnetration tested in the combined chronic toxicity/carcinogenicity study with rats; no adverse effects observed
Step 2) Modification of starting point	6/24	Correction of exposure duration in study (6 hrs/day) to default general population exposure (24 hrs/day)[1].
Step 3) Assessment factors
Interspecies	2.5	For inhalation studies only a factor 2.5 is used, and no correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements.
Intraspecies	10	As the general population includes the elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 10 is proposed in the REACH Guidance (R.8.4.3.1).
Exposure duration	1	No extrapolation of exposure duration is required, as NOAEL is based on the chronic study
Dose response	1
Quality of database	1
DNEL	Value
For general population	26000 x 6/24 / (2.5 x 10 x 1 x 1 x 1) =260 mg/m^3

[1] Since the general population covers the population living around the plant, a correction factor for an exposure duration of 24 hours is applied. There is no exposure to consumers since the polymer does not contain any free monomer and the polymer is still used for industrial uses and never into contact with the general consumers.