Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics
Type of information:
other: Statement
Adequacy of study:
key study
Study period:
2013-12-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expert Statement
Qualifier:
no guideline required
Details on absorption:
ASSESSMENT OF ABSORPTION

The assessment of potential absorption via oral/inhalation/dermal route was done according to REACH Guidance R7c. Additional literature data on tin sulfide is provided if available.

For detailed information please refer to the attached statement.

1 ORAL ABSORPTION

There are no data in literature on absorption of tin sulfide. Literature data on other inorganic Sn(II) and Sn(IV) salts is available describing that inorganic tin will hardly be absorbed after oral ingestion (summarized in ATSDR, 2005).

Taken together, based on the physical form and low water solubility, but mainly on the absence of toxicity in acute and repeated dose oral toxicity studies, oral absorption of tin sulfide is assumed to be very low. This conclusion is confirmed by the literature on oral absorption of inorganic tin compounds.

2 DERMAL ABSORPTION

Adequate data on uptake following dermal exposure appear to be lacking for tin sulfide or inorganic tin compounds (summarized in ATSDR, 2005).

Taken together, the physical state, the molecular weight, the water solubility, the vapour pressure, but mainly the absence of toxicity in acute dermal animal testing and the absence of irritating or corrosive and sensitizing potential the dermal absorption of tin sulfide is assumed to be very low.

3 RESPIRATORY ABSORPTION

Adequate data on uptake following respiratory exposure appear to be lacking for tin sulfide or inorganic tin compounds (summarized in ATSDR, 2005).

Taken together, even if the particle size and the low water solubility favour the assumption that particle can be absorbed on different stages of the stages of the respiratory tract the low vapour pressure and the tendency of tin sulfide particles to agglomerate and deposit do not favour the respiratory uptake.

Addtional assessment based on literature:
For the general population, the major source of tin is the diet. By comparison, drinking water and inhaled air contribute insignificant amounts. From data on mean tin intake from food for the populations of seven countries (Australia, France, Japan, Netherlands, New Zealand, the United Kingdom, and the USA), JECFA (2001) concluded that tin intakes ranged from < 1 up to 15 mg/person per day. Certain individuals who routinely consume canned fruits, vegetables, and juices from unlacquered cans could ingest 50-60 mg of tin daily (Johnson & Greger, 1982; Sherlock & Smart, 1984; JECFA, 2001). Those who consume about four servings of food stored in open unlacquered cans, on a daily basis, might consume in the region of 200 mg of tin per day (Greger & Baier, 1981; JECFA, 2001). In humans and laboratory mammals, absorption of inorganic tin from the gastrointestinal tract is low (generally less than 5 %), in particular for practically water insoluble compounds such as tin(ll) sulfide, but is influenced by dose, anion (compound solubility), and the presence of other substances. Unabsorbed ingested tin is mostly (95-99%) excreted in the faeces within 48 h. Absorbed tin distributes mainly to the bone, but also to the lungs, liver, and kidneys. Limited evidence suggests that inorganic tin does not readily cross the blood-brain barrier. Absorbed tin is mainly excreted in the urine, with some additional biliary excretion occurring. In mice, the biological half-life of absorbed inorganic tin was approximately 30 days. There is little or no evidence that practically water insoluble tin compounds pose any significant health risk at the exposure levels found in the work environment (European Commission, 2003).
Details on distribution in tissues:
ASSESSMENT OF DISTRIBUTION

For detailed information please refer to the attached statement.

The human body has been estimated to contain less than 17 mg of tin. However, literature describes that tin may accumulate in kidney, liver, lung and bone, thus, it has to be distributed (summarized in ATSDR, 2005). However, since the absorption of tin sulfide is assumed to be very low the distribution for this tin compound plays a minor role.

Taken together, based on the low water solubility, but mainly based on the absence of target organs or signs of toxicity in an acute and a repeated dose toxicity study with tin sulfide in rats up to the limit concentration, distribution was considered minimal. Even if literature describes that tin may accumulate in kidney, liver, lung and bone this is assumed to be of minor interest for tin sulfide due to the low absorption.
Details on excretion:
ASSESSMENT OF EXCRETION

For detailed information please refer to the attached statement.

Literature summarize that elimination of inorganic tin compounds from the body primarily takes place via faecal routes. Urine and bile appear to be major routes of the small amounts which are absorbed (summarized in ATSDR, 2005).

Taken together, the oral absorption of tin sulfide is very low, therefore the estimated favoured excretion route is the faecal route. However, very small quantities of absorbed and therefore dissolved parts are excreted via urine and bile. This is confirmed by literature.
Details on metabolites:
Adequate data on metabolism of tin sulfide or inorganic tin compounds appear to be lacking.

Reference:

ATSDR, Agency for Toxic Substances and Disease Registry, U.S. Department of health and human services (2005) Toxicological Profile for Tin and Tin Compounds

Conclusions:
Based on the physical form and low water solubility, but mainly on the absence of toxicity in acute and repeated dose oral toxicity studies, oral absorption of tin sulfide is assumed to be very low. This conclusion is confirmed by the literature on oral absorption of inorganic tin compounds.

The physical state, the molecular weight, the water solubility, the vapour pressure, but mainly the absence of toxicity in acute dermal animal testing and the absence of irritating or corrosive and sensitizing potential the dermal absorption of tin sulfide is assumed to be very low.

Even if the particle size and the low water solubility favour the assumption that particle can be absorbed on different stages of the stages of the respiratory tract the low vapour pressure and the tendency of tin sulfide particles to agglomerate and deposit do not favour the respiratory uptake.

Based on the low water solubility, but mainly based on the absence of target organs or signs of toxicity in an acute and a repeated dose toxicity study with tin sulfide in rats up to the limit concentration, distribution was considered minimal. Even if literature describes that tin may accumulate in kidney, liver, lung and bone this is assumed to be of minor interest for tin sulfide due to the low absorption.

There is no direct indication of relevant bioaccumulation potential of tin sulfide in lung, adipose tissue, bone or stratum corneum. However, literature describes that tin may accumulate in kidney, liver, lung and bone. Taking into account that absorption of tin sulfide is considered to be very low, accumulation is not considered to be relevant.

The oral absorption of tin sulfide is very low, therefore the estimated favoured excretion route is the faecal route. However, very small quantities of absorbed and therefore dissolved parts are excreted via urine and bile. This is confirmed by literature.

Description of key information

Basic Toxicokinetics assessment:

Based on the physical form and low water solubility, but mainly on the absence of toxicity in acute and repeated dose oral toxicity studies, oral absorption of tin sulfide is assumed to be very low. This conclusion is confirmed by the literature on oral absorption of inorganic tin compounds.

The physical state, the molecular weight, the water solubility, the vapour pressure, but mainly the absence of toxicity in acute dermal animal testing and the absence of irritating or corrosive and sensitizing potential the dermal absorption of tin sulfide is assumed to be very low.

Even if the particle size and the low water solubility favour the assumption that particle can be absorbed on different stages of the stages of the respiratory tract the low vapour pressure and the tendency of tin sulfide particles to agglomerate and deposit do not favour the respiratory uptake.

Based on the low water solubility, but mainly based on the absence of target organs or signs of toxicity in an acute and a repeated dose toxicity study with tin sulfide in rats up to the limit concentration, distribution was considered minimal. Even if literature describes that tin may accumulate in kidney, liver, lung and bone this is assumed to be of minor interest for tin sulfide due to the low absorption.

There is no direct indication of relevant bioaccumulation potential of tin sulfide in lung, adipose tissue, bone or stratum corneum. However, literature describes that tin may accumulate in kidney, liver, lung and bone. Taking into account that absorption of tin sulfide is considered to be very low, accumulation is not considered to be relevant.

The oral absorption of tin sulfide is very low, therefore the estimated favoured excretion route is the faecal route. However, very small quantities of absorbed and therefore dissolved parts are excreted via urine and bile. This is confirmed by literature.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
5
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
1

Additional information

Additional assessment based on literature of tin salts:

For the general population, the major source of tin is the diet. By comparison, drinking water and inhaled air contribute insignificant amounts. From data on mean tin intake from food for the populations of seven countries (Australia, France, Japan, Netherlands, New Zealand, the United Kingdom, and the USA), JECFA (2001) concluded that tin intakes ranged from < 1 up to 15 mg/person per day. Certain individuals who routinely consume canned fruits, vegetables, and juices from unlacquered cans could ingest 50-60 mg of tin daily (Johnson & Greger, 1982; Sherlock & Smart, 1984; JECFA, 2001). Those who consume about four servings of food stored in open unlacquered cans, on a daily basis, might consume in the region of 200 mg of tin per day (Greger & Baier, 1981; JECFA, 2001). In humans and laboratory mammals, absorption of inorganic tin from the gastrointestinal tract is low (generally less than 5 %), in particular for practically water insoluble compounds such as tin(ll) sulfide, but is influenced by dose, anion (compound solubility), and the presence of other substances. Unabsorbed ingested tin is mostly (95-99%) excreted in the faeces within 48 h. Absorbed tin distributes mainly to the bone, but also to the lungs, liver, and kidneys. Limited evidence suggests that inorganic tin does not readily cross the blood-brain barrier. Absorbed tin is mainly excreted in the urine, with some additional biliary excretion occurring. In mice, the biological half-life of absorbed inorganic tin was approximately 30 days. There is little or no evidence that practically water insoluble tin compounds pose any significant health risk at the exposure levels found in the work environment (European Commission, 2003).

Categories Display