Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.5 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.59 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.59 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Discussion and conclusion:

Read-across:

Reliable substance-specific information concerning the toxicity for tin difluoride does not exist. Instead, toxicological information on soluble fluoride (sodium and potassium) substances were extrapolated to tin (II) fluoride, at the same time considering the contribution of these counter ions as well as that of inorganic tin (II) substances as comparatively negligible. In essence, it is considered most appropriate to adopt toxicological threshold values established for “flourides” based on human data.

Effects of excessive exposure to fluorides on the skeletal system have been identified as the most sensitive endpoint. These effects include reduced bone strength, increased risk of fractures and/or skeletal fluorosis (stiffness of joints, skeletal deformities). For quite some time, the occupational exposure limit value for fluorides was set at 2.5 mg F/m³, e.g. SCOEL (1998), as supported by the findings by Derrberry et al. (1963) and Kaltreider et al. (1972). These authors had not reported effects on the skeletal system for workers exposed for 10 years to an average of 2.4 or 2.65 mg F/m³.

However, other and partly more recent human and animal data suggest that a limit value of 2.5 mg F/m³ may not be sufficient to protect humans against effects on the skeletal system: Assuming full absorption, and a shift-breathing volume of 10 m³ (per 8-hours), a worker working in an atmosphere containing 2.5 mg F/m³ would absorb 25 mg F/day. Further, as summarised above, the additional background fluoride intake from food, drinking water and dental care products may add up to a couple of mg F/day or even over 6 mg F/day in worst case scenarios, thus leading to worst case estimates of combined exposure of more than 30 mg F/day. In contrast, according to US DHHS (1991) and WHO (2002), skeletal fluorosis (clinical phase III) may result when exposed to 20 mg F/day for more than 20 years.

Multiple sources support the conclusion that a safe total daily intake of fluoride should at least be below ca. 14 mg F/day. EPA (1985) reported no skeletal fluorosis when fluoride in drinking waters was 4 mg F/L (i.e. ca. 8 mg F/day assuming a consumption of 2 litres/day).

The study by Li et al (2001) suggested no increased risk for bone fractures over 20 years at up to7.85 mg F/day, but increased risk for humans exposed to 14.13 mg F/day. The study by Hillier et al. (2000) in which no increase in the prevalence of hip fractures was seen at 0.2 - 0.3 mg F/day is considered supportive information.

The animal study by Turner et al. (2001) suggested a NOAEL for effects on bone density of 0.94 mg F/kgbw/day with a LOAEL at 3.2 mg F/kgbw/day. According to the authors, the NOAEL and LOAEL found in the rat study correspond to drinking waters concentrations for humans of 3 mg F/L and 10 mg F/L, respectively. Assuming a water intake of 2 L/day, these can be converted to corresponding daily doses of 6 mg F/day (NOAEL) and 20 mg F/day (LOAEL). Further, assuming a 10 m³ inhalation volume (for an 8 hour shift), these correspond to 0.6 mg F/m³ (NOAEC) and 2 mg F/m³ (LOAEC).

Based on these considerations, a workplace exposure limit (i.e. the DNEL) has been derived at 1 mg F/m³. As a worst case assumption, 100% systemic absorption may be assumed, which together with a 10 m³ shift breathing volume results in an estimated maximum daily dose at the workplace of 10 mg F/day. Note: it appears unrealistic to assume that a worker spends a full 8-hour shift in an atmosphere containing 1 mg F/m³. Further, depending for example on the particle size, not all particles will be inhaled (some will not be inhaled at all, others will be exhaled). On the other hand, there may be some contribution of fluorides absorbed via the skin (dermal exposure), or also of inadvertent ingestion (hand-to-mouth transfer). Whereas the latter cannot be quantified reliably and whereas such additional dermal and oral exposure would be expected on under circumstances of poor industrial hygiene, a 100% total systemic absorption is maintained, still presenting a conservative scenario for the risk assessment.

Acknowledging that background intake due to drinking water, food, dental care products etc. may exceed 5-6 mg F/day in highly worst case scenarios, a typical background intake would rather be in the of range of 0.5-2 mg F/day. Adding a worst case workplace exposure of 10 mg/day and a typical background exposure of 2 mg/day will still result in a safe total fluoride intake for workers.

Thus, the DNEL of 1 mg F/m³ is adequately protective, even when considering that workers can - in addition to the inhalation route - be further exposed to fluorides via other routes, i.e. dermal and/or oral (hand-to-mouth-transfer) at the workplace, and also due to a background intake via diet, drinking water and dental care products.

 

The application of assessment factors is not required in this assessment, for the following reasons:

-       Inter-species variability: Not required, since the assessment is based on human data

-       Intra-species variability: Not required, since the assessment is based data obtained in studies involving a sufficiently large number of subjects, thus intrinsically addressing intra-species variability

-       Exposure duration: Not required, since the studies are based on chronic exposure situations (continuous exposure via drinking waters, or occupational exposure for at least 10 years)

-       Dose response: Not required, since no-adverse-effect-levels were identified

-       Quality of whole data base: Not required, since the overall quality of the database is good, and findings are consistent

 

Biomonitoring

Urine biomonitoring has been shown to be an effective measure to control for safe systemic fluoride exposure levels in workers. Reference is made to the assessment by the German MAK commission (2006, with addendum 2007). MAK has established biological limit values for fluoride in the urine of workers as follows:

4.0 mg F / g creatinine, when sampled before the work shift

and/or

7.0 mg F / g creatinine, when sampled after an exposure period (or end-of-shift).

These limit values are based on the relationship between internal dose and health effects, and are applicable in addition or in parallel to the workplace air limit value of 1 mg F/m³.

 

References:

EFSA (2005): Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to the Tolerable Upper Intake Level of Fluoride (EFSA-Q-2003-018). EFSA Journal 192, 1-65.

MAK: (2006/2007): Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) in Germany: MAK and BAT value documentation for fluorides (in German Language). Original document dated 2006, supplemented by addendum in 2007.

SCOEL (1998): Recommendation from Scientific Committee on Occupational Exposure Limits for Fluorine, Hydrogen Fluoride and Inorganic Fluorides (not uranium hexafluoride). Document SCOEL/SUM 56.

US DHHS (1991): Review of Fluoride. Benefits and Risks. Ad Hoc Subcommittee on Fluoride, Committee to Coordinate Environmental Health and Related Programs, Washington DC, USA, Department of Health and Human Services.

US EPA (1985): Drinking water criteria document on fluoride (TR-832-5). NTIS, PB86-118163, ICAIR under EPA contract 68-03-3279.

WHO (2002):Environmental Health Criteria 227 on Fluorides.

 

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